                         SEQUENCE LISTING

<110>  REMD Biotherapeutics, Inc.
 
<120>  IMMUNOTHERAPY USING ANTIBODIES THAT BIND PROGRAMMED DEATH 1 
       (PD-1)

<130>  CACRE1.0013WO

<160>  72    

<170>  PatentIn version 3.5

<210>  1
<211>  288
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln 
1               5                   10                  15      


Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp 
            20                  25                  30          


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


Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 
    50                  55                  60                  


Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 
65                  70                  75                  80  


Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg 
                85                  90                  95      


Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 
            100                 105                 110         


Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 
        115                 120                 125             


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


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


Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly 
                165                 170                 175     


Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys 
            180                 185                 190         


Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro 
        195                 200                 205             


Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly 
    210                 215                 220                 


Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro 
225                 230                 235                 240 


Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly 
                245                 250                 255     


Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg 
            260                 265                 270         


Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 
        275                 280                 285             


<210>  2
<211>  5
<212>  PRT
<213>  Mus musculus

<400>  2

Asp Cys Trp Met His 
1               5   


<210>  3
<211>  5
<212>  PRT
<213>  Mus musculus

<400>  3

Arg Tyr Asp Met Ala 
1               5   


<210>  4
<211>  5
<212>  PRT
<213>  Mus musculus

<400>  4

Arg Tyr Gly Met Ser 
1               5   


<210>  5
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  5

Ala Ile Asp Thr Ser Asn Ser Tyr Thr Thr Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  6
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  6

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


Gly 
    


<210>  7
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  7

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


Gly 
    


<210>  8
<211>  8
<212>  PRT
<213>  Mus musculus

<400>  8

Ser Leu Gln Arg Pro Phe Asp Tyr 
1               5               


<210>  9
<211>  8
<212>  PRT
<213>  Mus musculus

<400>  9

Pro Tyr Tyr Tyr Ala Met Glu Tyr 
1               5               


<210>  10
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  10

Gln Glu Asp Ile Val Trp Phe Ala Tyr 
1               5                   


<210>  11
<211>  11
<212>  PRT
<213>  Mus musculus

<400>  11

Arg Ala Ser Glu Asn Val Tyr Ser Tyr Leu Ala 
1               5                   10      


<210>  12
<211>  11
<212>  PRT
<213>  Mus musculus

<400>  12

Lys Ala Ser Gln Asp Val Asp Thr Ala Val Ala 
1               5                   10      


<210>  13
<211>  15
<212>  PRT
<213>  Mus musculus

<400>  13

Arg Ala Ser Glu Ser Val Asp Asn Ser Gly Leu Ser Phe Met Asn 
1               5                   10                  15  


<210>  14
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  14

Asn Ala Lys Thr Leu Thr Gly 
1               5           


<210>  15
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  15

Trp Ala Ser Thr Arg His Thr 
1               5           


<210>  16
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  16

Ala Ala Ser Asn Gln Gly Ser 
1               5           


<210>  17
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  17

Leu Gln His Tyr Gly Tyr Pro Phe Thr 
1               5                   


<210>  18
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  18

Gln Gln Tyr Ser Thr Phe Pro Trp Thr 
1               5                   


<210>  19
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  19

Gln Gln Ser Lys Glu Val Pro Trp Thr 
1               5                   


<210>  20
<211>  117
<212>  PRT
<213>  Mus musculus

<400>  20

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


Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Ile Thr Asp Cys 
            20                  25                  30          


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


Gly Ala Ile Asp Thr Ser Asn Ser Tyr Thr Thr Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Lys Gly Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Ile Ser Leu Gln Arg Pro Phe Asp Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Leu Thr Val Ser Ser 
        115         


<210>  21
<211>  351
<212>  DNA
<213>  Mus musculus

<400>  21
caggtccaac tgcagcagcc tggggctgag cttgtgatgc ctggggcttc agtgaagatg       60

tcctgtaagg cttcgggcta cacaatcact gactgctgga tgcactgggt gaagcagagg      120

cctggacaag gccttgagtg gatcggagcg attgatactt ctaatagtta tactacttac      180

aatcaaaagt tcaagggcaa ggccacattg actgtagacg aatcctccag cacagcctac      240

atgcagttca acagcctgac atctgacgac tctgcggtct atttctgtgc aatttcctta      300

caacggccgt ttgactactg gggccaaggc accactctca cagtctcctc a               351


<210>  22
<211>  117
<212>  PRT
<213>  Mus musculus

<400>  22

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


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


Asp Met Ala Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


Ala Phe Ile Ser Gly Gly Gly Ser Asn 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 Thr Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Ser 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  23
<211>  351
<212>  DNA
<213>  Mus musculus

<400>  23
gaagtgcagc tggtggagtc tgggggagac ttagtcaagc ctggagggtc cctgaaactc       60

tcctgtgcag cctctggatt cgttttcagt aggtatgaca tggcctgggt tcgccagact      120

ccggagaaga ggctggagtg ggtcgcattc attagtggtg gtggttctaa tacctactat      180

ccagacactg tgaagggccg attcaccatc tccagagaca atgccaagaa caccctgtac      240

ctgcaaatga ccagtctgaa gtctgaggac acagccgtgt attattgtat aagtccctac      300

tactatgcta tggaatattg gggtcaagga acctcagtca ccgtctcctc a               351


<210>  24
<211>  118
<212>  PRT
<213>  Mus musculus

<400>  24

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


Ser Leu Lys Val Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Arg 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 Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Asn 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      


Val Arg Gln Glu Asp Ile Val Trp Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ala 
        115             


<210>  25
<211>  354
<212>  DNA
<213>  Mus musculus

<400>  25
gaagtgaggc tggtggagtc tgggggaggc ttagtgaagc ctggagggtc cctgaaagtc       60

tcctgtgtag cctctggatt cactttcagt aggtatggca tgtcttgggt tcgccagact      120

ccggagaaga ggctggagtg ggtcgcaacc attagtggtg gtggtcgtga cacctactat      180

ccagacagtg tgaaggggcg attcaccata tccagagaca atgccaagaa caatttgtat      240

ctgcaaatga gtagtctgag gtctgaggac acggccttgt attactgtgt aagacaggag      300

gacatcgtct ggtttgctta ctggggccaa gggactctgg tcactgtctc tgca            354


<210>  26
<211>  107
<212>  PRT
<213>  Mus musculus

<400>  26

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


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


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


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


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


Glu Asp Phe Gly Ser Tyr Tyr Cys Leu Gln His Tyr Gly Tyr Pro Phe 
                85                  90                  95      


Thr Phe Gly Ser Gly Thr Lys Leu Glu Lys Lys 
            100                 105         


<210>  27
<211>  321
<212>  DNA
<213>  Mus musculus

<400>  27
gacatccaga tgactcagtc tccagcctcc ctatctgcat ctgtgggaga aaatgtcacc       60

atcacatgtc gagcaagtga gaatgtttac agttatttag catggtatca gcagaaagag      120

ggaaaatctc ctcagctcct ggtctataat gcaaaaacgt taacaggagg tgtgccatca      180

aggttcagtg gcagtggatc aggtacacag ttttctctga ggatcagcag cctgcagcct      240

gaagattttg gtagttatta ctgtctacag cattatggtt atccattcac gttcggctcg      300

gggacaaagt tggaaaaaaa a                                                321


<210>  28
<211>  107
<212>  PRT
<213>  Mus musculus

<400>  28

Asp Ile Val Met Thr Gln Ser His Lys Phe Ile Ser Thr Ser Val Gly 
1               5                   10                  15      


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 
    50                  55                  60                  


Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Leu Ser Asn Val Gln Ser 
65                  70                  75                  80  


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


Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys 
            100                 105         


<210>  29
<211>  321
<212>  DNA
<213>  Mus musculus

<400>  29
gacattgtga tgacccagtc tcacaaattc atatccacat cagtaggaga cagggtcagc       60

atcacctgca aggccagtca ggatgtggat actgctgtag cctggtatca acagaaacca      120

gggcaatctc ctaaattatt gattcactgg gcatccaccc gacacacagg agtccctgat      180

cgcttcacag ggggtggatc tgggacagat ttcactctca cccttagcaa tgtgcagtct      240

gaagacttgg cagattattt ctgtcagcaa tacagcacct ttccgtggac gttcggtgga      300

ggcaccaggc tggaaatcaa g                                                321


<210>  30
<211>  111
<212>  PRT
<213>  Mus musculus

<400>  30

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 Asn Ser 
            20                  25                  30          


Gly Leu Ser Phe Met Asn Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


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


<210>  31
<211>  333
<212>  DNA
<213>  Mus musculus

<400>  31
gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc       60

atctcctgca gagccagcga aagtgttgat aattctggcc ttagttttat gaactggttc      120

caacagaaac caggacagcc acccaaactc ctcatctatg ctgcttccaa ccaaggatcc      180

ggggtccctg ccaggtttag tggcagtggg tctgggacag acttcagcct caacatccat      240

tctatggagg aggatgatac tgcaatatat ttctgtcagc aaagtaagga ggttccgtgg      300

acgttcggtg gaggcaccaa gttggaaatc aaa                                   333


<210>  32
<211>  463
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain of a chimeric antibody that binds PD-1 - 19 aa leader
       sequence

<400>  32

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


Val His Ser Glu Val Gln Leu Val Glu Ser Gly Gly Asp Leu Val Lys 
            20                  25                  30          


Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Val Phe 
        35                  40                  45              


Ser Arg Tyr Asp Met Ala Trp Val Arg Gln Thr Pro Glu Lys Arg Leu 
    50                  55                  60                  


Glu Trp Val Ala Phe Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Pro 
65                  70                  75                  80  


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


Thr Leu Tyr Leu Gln Met Thr Ser Leu Lys Ser Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln 
        115                 120                 125             


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


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


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
                165                 170                 175     


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


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


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


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


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


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


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        275                 280                 285             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    290                 295                 300                 


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


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


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


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


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


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


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


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        435                 440                 445             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    450                 455                 460             


<210>  33
<211>  1389
<212>  DNA
<213>  Artificial

<220>
<223>  Heavy chain of a chimeric antibody that binds PD-1 - 19 aa leader
       sequence

<400>  33
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgaa       60

gtgcagctgg tggagtccgg gggcgatctg gtcaaacctg gagggagcct gaaactgtct      120

tgtgccgcat ctggattcgt cttttccaga tatgacatgg cctgggtgag gcagacccca      180

gagaagcgcc tggagtgggt ggccttcatc tctggcggcg gcagcaacac atactatccc      240

gacaccgtga agggccggtt tacaatcagc agagataacg ccaagaatac actgtatctg      300

cagatgacct ctctgaagag cgaggatacc gccgtgtact attgcatctc tccttactat      360

tacgccatgg agtactgggg ccagggcaca agcgtgaccg tgagctccgc ctccacaaag      420

ggaccaagcg tgttcccact ggcaccatgc tctcgcagca catccgagtc taccgccgcc      480

ctgggatgtc tggtgaagga ctacttccct gagccagtga ccgtgtcctg gaacagcggc      540

gccctgacat ccggagtgca cacctttcca gccgtgctgc agtctagcgg cctgtatagc      600

ctgtcctctg tggtgacagt gcccagctcc tctctgggca ccaagacata cacctgcaac      660

gtggaccaca agcctagcaa taccaaggtg gataagcggg tggagtccaa gtatggacca      720

ccttgcccac catgtccagc acctgagttt ctgggaggac catccgtgtt cctgtttcct      780

ccaaagccta aggacacact gatgatctcc agaacacctg aggtgacctg cgtggtggtg      840

gacgtgtctc aggaggatcc agaggtgcag ttcaactggt acgtggatgg cgtggaggtg      900

cacaatgcca agaccaagcc cagggaggag cagtttaaca gcacatatcg cgtggtgtcc      960

gtgctgaccg tgctgcacca ggattggctg aacggcaagg agtacaagtg caaggtgagc     1020

aataagggcc tgcctagctc catcgagaag acaatctcca aggcaaaggg acagcctagg     1080

gagccacagg tgtataccct gcccccttct caggaggaga tgacaaagaa ccaggtgagc     1140

ctgacctgtc tggtgaaggg cttctaccca tccgacatcg ccgtggagtg ggagtctaat     1200

ggccagcccg agaacaatta taagaccaca ccacccgtgc tggacagcga tggctccttc     1260

tttctgtact ctcggctgac cgtggataag agcagatggc aggagggcaa cgtgttcagc     1320

tgttccgtga tgcacgaagc actgcacaat cattacactc agaaaagcct gtcactgtcc     1380

ctgggcaaa                                                             1389


<210>  34
<211>  233
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain of a chimeric antibody that binds PD-1 - 19 aa leader
       sequence

<400>  34

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


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


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


Asp Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys 
    50                  55                  60                  


Leu Leu Ile His Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg 
65                  70                  75                  80  


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


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


Phe Pro Trp Thr Phe Gly Gly Gly Thr Arg Leu 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>  35
<211>  699
<212>  DNA
<213>  Artificial

<220>
<223>  Light chain of a chimeric antibody that binds PD-1 - 19 aa leader
       sequence

<400>  35
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgat       60

attgtgatga ctcagagcca taagtttatt tctaccagtg tcggggatcg tgtctccatt      120

acttgtaagg cttcccagga tgtggacacc gccgtggctt ggtaccagca gaagcccggc      180

cagtccccta aactgctgat ccactgggca tctactaggc acaccggagt gccagaccgg      240

ttcacaggcg gaggaagcgg gactgacttc accctgacac tgtctaacgt ccagagtgag      300

gacctggccg attacttctg tcagcagtat tcaaccttcc cttggacctt cggggggggt      360

acacggctgg aaatcaaacg tactgtggct gcaccatctg tcttcatctt cccgccatct      420

gatgagcagt tgaaatctgg aactgcctct gtggtgtgcc tgctgaataa cttctatccc      480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag      540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg      600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg      660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt                             699


<210>  36
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  36

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ser Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  37
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  37

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


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


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


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


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


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


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


<210>  38
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  38

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ala Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  39
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  39

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  40
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  40

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ser Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  41
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  41

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ala Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  42
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  42

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ser Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  43
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  43

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  44
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  44

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  45
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  45

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  46
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  46

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


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


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


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


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  47
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  47

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  48
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  48

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  49
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  49

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  50
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  50

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  51
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  51

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  52
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  52

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


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


<210>  53
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region of a humanized antibody that binds 
       PD-1

<400>  53

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 Val Phe Ser Arg Tyr 
            20                  25                  30          


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


Ser Phe Ile Ser Gly Gly Gly Ser Asn 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 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln Gly Thr Thr 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  54
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  54

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


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


<210>  55
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  55

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


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


<210>  56
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  56

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


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


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


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


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


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


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


<210>  57
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region of a humanized antibody that binds 
       PD-1

<400>  57

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


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


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


His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  58
<211>  463
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  58

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


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


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


Ser Arg Tyr Asp Met Ala Trp Val Arg Gln Thr Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ala Phe Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Pro 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln 
        115                 120                 125             


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


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


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
                165                 170                 175     


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


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


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


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


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


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


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        275                 280                 285             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    290                 295                 300                 


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


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


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


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


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


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


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


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        435                 440                 445             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    450                 455                 460             


<210>  59
<211>  1389
<212>  DNA
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  59
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgag       60

gtgcagctgg tggaatctgg ggggggactg gtgcagcctg gaggaagcct gagactgtct      120

tgtgccgcat ctgggtttgt gttctccaga tacgacatgg catgggtgcg ccagacccca      180

ggcaagggcc tggagtgggt ggccttcatc agcggaggag gatccaacac ctactatcct      240

gacacagtga agggccggtt taccatctct agagataaca gcaagaatac actgtatctg      300

cagatgaaca gcctgcgggc cgaggataca gccgtgtact attgcatctc accttactac      360

tacgcaatgg aatactgggg acaggggact accgtcaccg tctcctcagc ctctacaaag      420

ggcccctccg tgtttccact ggctccctgc agcaggtcta catccgagag caccgctgct      480

ctgggatgtc tggtgaagga ttacttccct gagccagtga ccgtgagctg gaactccgga      540

gctctgacat ccggagtgca cacctttcct gctgtgctgc agagctctgg cctgtacagc      600

ctgtccagcg tggtgacagt gccatcttcc agcctgggca ccaagacata tacctgcaac      660

gtggaccata agcccagcaa taccaaggtg gataagagag tggagtctaa gtacggacca      720

ccttgcccac catgtccagc tcctgagttt ctgggaggac catccgtgtt cctgtttcct      780

ccaaagccta aggacaccct gatgatctct cgcacacccg aggtgacctg tgtggtggtg      840

gacgtgtccc aggaggatcc tgaggtgcag ttcaactggt acgtggatgg cgtggaggtg      900

cacaatgcta agaccaagcc tagggaggag cagtttaaca gcacataccg ggtggtgtct      960

gtgctgaccg tgctgcatca ggactggctg aacggcaagg agtataagtg caaggtgagc     1020

aataagggcc tgccatcttc catcgagaag acaatctcta aggctaaggg acagcctagg     1080

gagccacagg tgtacaccct gcccccttcc caggaggaga tgacaaagaa ccaggtgagc     1140

ctgacctgtc tggtgaaggg cttctatcct tctgacatcg ctgtggagtg ggagtccaat     1200

ggccagccag agaacaatta caagaccaca ccacccgtgc tggactccga tggcagcttc     1260

tttctgtatt ccaggctgac cgtggataag agccggtggc aggagggcaa tgtgttttct     1320

tgttccgtga tgcacgaagc actgcacaac cactacactc agaagtccct gtcactgtcc     1380

ctgggcaag                                                             1389


<210>  60
<211>  233
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  60

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


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


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


Asp Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys 
    50                  55                  60                  


Leu Leu Ile His Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg 
65                  70                  75                  80  


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


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


Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu 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>  61
<211>  699
<212>  DNA
<213>  Artificial

<220>
<223>  Light chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  61
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgac       60

attcagatga cccagagccc ttcaagtatt agcacctcag tcggggatag agtcacaatc      120

acctgtaaag ccagccagga cgtggacacc gcagtggcat ggtaccagca gaagcctggc      180

aagtccccta agctgctgat ccactgggca tctaccaggc acacaggagt gccaagcaga      240

ttctctggca gcggctccgg cacagatttt accctgacac tgagctccgt gcagccagag      300

gacctggcag attatttctg tcagcagtat tcaaccttcc cttggacctt cggcggaggc      360

actaaactgg agatcaaacg aacggtggct gcaccatctg tcttcatctt cccgccatct      420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc      480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag      540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg      600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg      660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt                             699


<210>  62
<211>  463
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  62

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


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


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


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


Glu Trp Val Ser Phe Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Pro 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln 
        115                 120                 125             


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


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


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
                165                 170                 175     


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


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


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


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


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


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


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        275                 280                 285             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    290                 295                 300                 


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


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


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


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


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


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


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


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        435                 440                 445             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    450                 455                 460             


<210>  63
<211>  1389
<212>  DNA
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  63
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgag       60

gtgcagctgg tggaatctgg ggggggactg gtgcagcctg gaggaagcct gagactgtct      120

tgtgccgcat ctgggtttgt gttctccaga tacgacatgg catgggtgcg ccaggcacca      180

ggcaagggcc tggagtgggt gagcttcatc agcggaggag gatccaacac ctactatcct      240

gacacagtga agggccggtt taccatctct agagataaca gcaagaatac actgtatctg      300

cagatgaaca gcctgcgggc cgaggataca gccgtgtact attgcatctc accttactac      360

tacgcaatgg aatactgggg acaggggact accgtcaccg tctcctcagc ctctacaaag      420

ggcccctccg tgtttccact ggctccctgc agcaggtcta catccgagag caccgctgct      480

ctgggatgtc tggtgaagga ttacttccct gagccagtga ccgtgagctg gaactccgga      540

gctctgacat ccggagtgca cacctttcct gctgtgctgc agagctctgg cctgtacagc      600

ctgtccagcg tggtgacagt gccatcttcc agcctgggca ccaagacata tacctgcaac      660

gtggaccata agcccagcaa taccaaggtg gataagagag tggagtctaa gtacggacca      720

ccttgcccac catgtccagc tcctgagttt ctgggaggac catccgtgtt cctgtttcct      780

ccaaagccta aggacaccct gatgatctct cgcacacccg aggtgacctg tgtggtggtg      840

gacgtgtccc aggaggatcc tgaggtgcag ttcaactggt acgtggatgg cgtggaggtg      900

cacaatgcta agaccaagcc tagggaggag cagtttaaca gcacataccg ggtggtgtct      960

gtgctgaccg tgctgcatca ggactggctg aacggcaagg agtataagtg caaggtgagc     1020

aataagggcc tgccatcttc catcgagaag acaatctcta aggctaaggg acagcctagg     1080

gagccacagg tgtacaccct gcccccttcc caggaggaga tgacaaagaa ccaggtgagc     1140

ctgacctgtc tggtgaaggg cttctatcct tctgacatcg ctgtggagtg ggagtccaat     1200

ggccagccag agaacaatta caagaccaca ccacccgtgc tggactccga tggcagcttc     1260

tttctgtatt ccaggctgac cgtggataag agccggtggc aggagggcaa tgtgttttct     1320

tgttccgtga tgcacgaagc actgcacaac cactacactc agaagtccct gtcactgtcc     1380

ctgggcaag                                                             1389


<210>  64
<211>  233
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  64

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


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


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


Asp Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
    50                  55                  60                  


Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser 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 Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Thr 
            100                 105                 110         


Phe Pro Trp Thr Phe Gly Gly 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>  65
<211>  699
<212>  DNA
<213>  Artificial

<220>
<223>  Light chain fo ahumanized antibody that binds PD-1 - 19 aa leader
       sequence

<400>  65
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgac       60

attcagatga ctcagagccc ttcaagcgtg tcagcaagcg tgggcgacag ggtcaccatc      120

acatgcaaag cctctcagga tgtggacacc gcagtcgcct ggtatcagca gaagcctggg      180

aaagctccaa agctgctgat ctactgggca agtacacggc acactggagt gccttccaga      240

ttctccggct ctgggagtgg aacagacttt actctgacca tcagcagcct ccagcccgag      300

gacttcgcta cctactattg tcagcagtac agcacatttc cttggacttt tggcggggga      360

accaaagtgg aaatcaagcg aacggtggct gcaccatctg tcttcatctt cccgccatct      420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc      480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag      540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg      600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg      660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt                             699


<210>  66
<211>  463
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  66

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


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


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


Ser Arg Tyr Asp Met Ala Trp Val Arg Gln Thr Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ser Phe Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Pro 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ile Ser Pro Tyr Tyr Tyr Ala Met Glu Tyr Trp Gly Gln 
        115                 120                 125             


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


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


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
                165                 170                 175     


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


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


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


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


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


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


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        275                 280                 285             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    290                 295                 300                 


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


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


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


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


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


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


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


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        435                 440                 445             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    450                 455                 460             


<210>  67
<211>  1389
<212>  DNA
<213>  Artificial

<220>
<223>  Heavy chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  67
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgag       60

gtgcagctgg tggaaagtgg agggggactg gtgcagcccg gagggagcct gagactgagt      120

tgtgccgcaa gtggattcgt gttctcaaga tacgacatgg catgggtgcg ccagacacca      180

ggcaagggac tggagtgggt cagcttcatc tccggcgggg gaagcaacac ctactatcct      240

gacacagtga agggccggtt tactatctct agagataaca gtaagaacac cctgtatctg      300

cagatgaatt ctctgcgagc cgaagatacc gctgtctact attgcatctc accttattat      360

tacgctatgg agtattgggg acagggaaca acagtcaccg tcagcagcgc ctctacaaag      420

ggcccctccg tgtttccact ggctccctgc agcaggtcta catccgagag caccgctgct      480

ctgggatgtc tggtgaagga ttacttccct gagccagtga ccgtgagctg gaactccgga      540

gctctgacat ccggagtgca cacctttcct gctgtgctgc agagctctgg cctgtacagc      600

ctgtccagcg tggtgacagt gccatcttcc agcctgggca ccaagacata tacctgcaac      660

gtggaccata agcccagcaa taccaaggtg gataagagag tggagtctaa gtacggacca      720

ccttgcccac catgtccagc tcctgagttt ctgggaggac catccgtgtt cctgtttcct      780

ccaaagccta aggacaccct gatgatctct cgcacacccg aggtgacctg tgtggtggtg      840

gacgtgtccc aggaggatcc tgaggtgcag ttcaactggt acgtggatgg cgtggaggtg      900

cacaatgcta agaccaagcc tagggaggag cagtttaaca gcacataccg ggtggtgtct      960

gtgctgaccg tgctgcatca ggactggctg aacggcaagg agtataagtg caaggtgagc     1020

aataagggcc tgccatcttc catcgagaag acaatctcta aggctaaggg acagcctagg     1080

gagccacagg tgtacaccct gcccccttcc caggaggaga tgacaaagaa ccaggtgagc     1140

ctgacctgtc tggtgaaggg cttctatcct tctgacatcg ctgtggagtg ggagtccaat     1200

ggccagccag agaacaatta caagaccaca ccacccgtgc tggactccga tggcagcttc     1260

tttctgtatt ccaggctgac cgtggataag agccggtggc aggagggcaa tgtgttttct     1320

tgttccgtga tgcacgaagc actgcacaac cactacactc agaagtccct gtcactgtcc     1380

ctgggcaag                                                             1389


<210>  68
<211>  233
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  68

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


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


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


Asp Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys 
    50                  55                  60                  


Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser 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 Gln Pro Glu Asp Phe Ala Asp Tyr Phe Cys Gln Gln Tyr Ser Thr 
            100                 105                 110         


Phe Pro Trp Thr Phe Gly Gly 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>  69
<211>  699
<212>  DNA
<213>  Artificial

<220>
<223>  Light chain of a humanized antibody that binds PD-1 - 19 aa 
       leader sequence

<400>  69
atgggctgga gctggatcct gctgttcctc ctgagcgtga cagcaggagt gcacagcgac       60

atccagatga cccagtctcc ctcaagcatt tcaacctcag tcggcgatag agtgaccatt      120

acctgcaagg caagccagga cgtggacaca gccgtggctt ggtaccagca gaagcccggc      180

aaaagtccta agctgctgat ctattgggca agcactcggc acaccggggt cccatccaga      240

ttctctggca gtgggtcagg aaccgatttt accctgacaa ttagctccct gcagcccgag      300

gacttcgccg attacttttg tcagcagtat tcaacatttc cctggacttt cggcgggggc      360

accaaggtcg agattaagcg aacggtggct gcaccatctg tcttcatctt cccgccatct      420

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc      480

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag      540

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg      600

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg      660

agctcgcccg tcacaaagag cttcaacagg ggagagtgt                             699


<210>  70
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  70

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


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


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  71
<211>  106
<212>  PRT
<213>  Homo sapiens

<400>  71

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


Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 
            20                  25                  30          


Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 
        35                  40                  45              


Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn 
    50                  55                  60                  


Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 
65                  70                  75                  80  


Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 
                85                  90                  95      


Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 
            100                 105     


<210>  72
<211>  327
<212>  PRT
<213>  Homo sapiens

<400>  72

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
1               5                   10                  15      


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


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


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
65                  70                  75                  80  


Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                165                 170                 175     


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
        195                 200                 205             


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
225                 230                 235                 240 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
    290                 295                 300                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
305                 310                 315                 320 


Leu Ser Leu Ser Leu Gly Lys 
                325         


