                         SEQUENCE LISTING

<110>  Macrogenics, Inc.
       Wigginton, Jon Marc
       Pandya, Naimish Bharat
       Lechleider, Robert Joseph
       Koenig, Scott
       Bonvini, Ezio
 
<120>  Combination Therapy for the Treatment of Cancer

<130>  1301.0120PCT

<150>  US 62/175,039
<151>  2015-06-12

<150>  US 62/211,109
<151>  2015-08-28

<160>  87    

<170>  PatentIn version 3.5

<210>  1
<211>  645
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding light chain of preferred Variant Chimeric
       4D5 Antibodies

<400>  1
gacatcgtga tgacccagtc ccacaagttc atgtccacct ctgtgggcga tagggtcagc       60

atcacctgca aggccagcca ggatgtgaat actgctgtag cctggtatca gcagaaacca      120

ggacattctc ccaaactgct gatttactcc gcatccttcc ggtacactgg agtccctgat      180

cgcttcactg gcagcagatc tgggacagat ttcactttca ccatcagcag tgtgcaggct      240

gaagacctgg cagtttatta ctgtcagcaa cattatacta cacctcccac cttcggaggg      300

ggtaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca      360

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat      420

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag      480

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg      540

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc      600

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag                      645


<210>  2
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain of preferred Variant Chimeric 4D5 Antibodies

<400>  2

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


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


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


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


Ser Arg Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala 
65                  70                  75                  80  


Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
                85                  90                  95      


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


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


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


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  3
<211>  107
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  Light Chain Variable Domain of Murine 4D5 Antibody

<400>  3

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


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


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


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


Asn Arg Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala 
65                  70                  75                  80  


Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
                85                  90                  95      


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


<210>  4
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 4D5 VL region

<400>  4

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


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


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


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


Ser Arg Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala 
65                  70                  75                  80  


Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
                85                  90                  95      


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


<210>  5
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light Chain Variable Domain of Humanized 4D5 Antibody

<400>  5

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn 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 Ser Ala Ser Phe Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg 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 His Tyr Thr Thr Pro Pro 
                85                  90                  95      


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


<210>  6
<211>  1353
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding Chimeric 4D5 heavy chain having a  
       wild-type Fc Region

<400>  6
caggttcagc tgcagcagtc tggccctgag ctggtgaagc caggggcctc actcaagttg       60

tcctgtacag cttctggctt caacatcaaa gacacctata tccactgggt gaaacagagg      120

cctgaacagg gcctggaatg gattggaagg atttatccta ccaatggcta tactagatat      180

gacccaaagt tccaggacaa ggccactatc acagcagaca catcctccaa cacagcctac      240

ctgcaagtca gccgcctgac atctgaggac actgccgtct attactgctc ccggtgggga      300

ggggacggct tctatgctat ggactactgg ggtcagggag cctccgtgac cgtgagctcc      360

gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      420

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      480

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc      660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      720

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      780

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      840

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac      900

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag      960

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1020

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1080

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1140

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1200

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1260

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1320

cagaagagcc tctccctgtc tccgggtaaa tga                                  1353


<210>  7
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 4D5 heavy chain having a  wild-type Fc Region

<400>  7

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


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


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


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


Gln Asp Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 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 Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


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


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


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


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


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  8
<211>  1353
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding heavy chain of a Variant Chimeric 4D5 
       Antibody having the FcMT1 variant Fc Region

<400>  8
caggttcagc tgcagcagtc tggccctgag ctggtgaagc caggggcctc actcaagttg       60

tcctgtacag cttctggctt caacatcaaa gacacctata tccactgggt gaaacagagg      120

cctgaacagg gcctggaatg gattggaagg atttatccta ccaatggcta tactagatat      180

gacccaaagt tccaggacaa ggccactatc acagcagaca catcctccaa cacagcctac      240

ctgcaagtca gccgcctgac atctgaggac actgccgtct attactgctc ccggtgggga      300

ggggacggct tctatgctat ggactactgg ggtcagggag cctccgtgac cgtgagctcc      360

gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      420

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      480

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc      660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      720

ccgtcagtct tcctcttacc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      780

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      840

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgccggagga gcagtacaac      900

agcacgctcc gtgtggtcag catcctcacc gtcctgcacc aggactggct gaatggcaag      960

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1020

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1080

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1140

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctctcgtg     1200

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1260

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1320

cagaagagcc tctccctgtc tccgggtaaa tga                                  1353


<210>  9
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of a Variant Chimeric 4D5 Antibody having the FcMT1 
       variant Fc Region

<400>  9

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


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


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


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


Gln Asp Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 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 Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


Asn Ala Lys Thr Lys Pro Pro Glu Glu Gln Tyr Asn Ser Thr Leu Arg 
    290                 295                 300                 


Val Val Ser Ile Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


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


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  10
<211>  1353
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding heavy chain of a Variant Chimeric 4D5 
       Antibody having the FcMT2 variant Fc Region

<400>  10
caggttcagc tgcagcagtc tggccctgag ctggtgaagc caggggcctc actcaagttg       60

tcctgtacag cttctggctt caacatcaaa gacacctata tccactgggt gaaacagagg      120

cctgaacagg gcctggaatg gattggaagg atttatccta ccaatggcta tactagatat      180

gacccaaagt tccaggacaa ggccactatc acagcagaca catcctccaa cacagcctac      240

ctgcaagtca gccgcctgac atctgaggac actgccgtct attactgctc ccggtgggga      300

ggggacggct tctatgctat ggactactgg ggtcagggag cctccgtgac cgtgagctcc      360

gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      420

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      480

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc      660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cgtgggggga      720

ccgtcagtct tcctcttacc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      780

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      840

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgccggagga gcagtacaac      900

agcacgctcc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag      960

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1020

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1080

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1140

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctctcgtg     1200

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1260

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1320

cagaagagcc tctccctgtc tccgggtaaa tga                                  1353


<210>  11
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of a Variant Chimeric 4D5 Antibody having the FcMT2 
       variant Fc Region

<400>  11

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


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


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


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


Gln Asp Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 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 Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Val Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


Asn Ala Lys Thr Lys Pro Pro Glu Glu Gln Tyr Asn Ser Thr Leu Arg 
    290                 295                 300                 


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


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


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


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  12
<211>  1353
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding Variant Chimeric 4D5 Antibody having the 
       FcMT3 variant Fc Region

<400>  12
caggttcagc tgcagcagtc tggccctgag ctggtgaagc caggggcctc actcaagttg       60

tcctgtacag cttctggctt caacatcaaa gacacctata tccactgggt gaaacagagg      120

cctgaacagg gcctggaatg gattggaagg atttatccta ccaatggcta tactagatat      180

gacccaaagt tccaggacaa ggccactatc acagcagaca catcctccaa cacagcctac      240

ctgcaagtca gccgcctgac atctgaggac actgccgtct attactgctc ccggtgggga      300

ggggacggct tctatgctat ggactactgg ggtcagggag cctccgtgac cgtgagctcc      360

gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      420

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      480

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc      660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      720

ccgtcagtct tcctcttacc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      780

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      840

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgccggagga gcagtacaac      900

agcacgctcc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag      960

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1020

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1080

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1140

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1200

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1260

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1320

cagaagagcc tctccctgtc tccgggtaaa tga                                  1353


<210>  13
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Variant Chimeric 4D5 Antibody having the FcMT3 variant Fc Region


<220>
<221>  MISC_FEATURE
<222>  (1)..(450)
<223>  Variant Chimeric 4D5 Antibody having the FcMT3 variant Fc Region

<400>  13

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


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


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


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


Gln Asp Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 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 Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


Asn Ala Lys Thr Lys Pro Pro Glu Glu Gln Tyr Asn Ser Thr Leu Arg 
    290                 295                 300                 


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


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


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


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  14
<211>  288
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(288)
<223>  Human PD-1

<400>  14

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>  15
<211>  113
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(113)
<223>  heavy chain variable domain of PD-1 mAb 1

<400>  15

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


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


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


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


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


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


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


Ser 
    


<210>  16
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  CDRH1 of PD-1 mAb 1

<400>  16

Asn Ser Gly Met His 
1               5   


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


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  CDRH2 of PD-1 mAb 1

<400>  17

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


Gly 
    


<210>  18
<211>  4
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(4)
<223>  CDRH3 of PD-1 mAb 1

<400>  18

Asn Asp Asp Tyr 
1               


<210>  19
<211>  107
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  light chain variable domain of PD-1 mAb 1

<400>  19

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


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


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


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


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


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


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


<210>  20
<211>  11
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(11)
<223>  CDRL1 of PD-1 mAb 1

<400>  20

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


<210>  21
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  CDRL2 of PD-1 mAb 1

<400>  21

Asp Ala Ser Asn Arg Ala Thr 
1               5           


<210>  22
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  CDRL3 of PD-1 mAb 1

<400>  22

Gln Gln Ser Ser Asn Trp Pro Arg Thr 
1               5                   


<210>  23
<211>  120
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(120)
<223>  heavy chain variable domain of PD-1 mAb 2

<400>  23

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


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


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


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  24
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 2 CDR1

<400>  24

Asn Tyr Tyr Met Tyr 
1               5   


<210>  25
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  heavy chain variable domain of PD-1 mAb 2 CDR2

<400>  25

Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys 
1               5                   10                  15      


Asn 
    


<210>  26
<211>  11
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(11)
<223>  heavy chain variable domain of PD-1 mAb 2 CDR3

<400>  26

Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr 
1               5                   10      


<210>  27
<211>  111
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(111)
<223>  light chain variable domain of PD-1 mAb 2

<400>  27

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


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


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


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


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


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


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


<210>  28
<211>  15
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(15)
<223>  light chain variable domain of PD-1 mAb 2 CDR1

<400>  28

Arg Ala Ser Lys Gly Val Ser Thr Ser Gly Tyr Ser Tyr Leu His 
1               5                   10                  15  


<210>  29
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  light chain variable domain of PD-1 mAb 2 CDR2

<400>  29

Leu Ala Ser Tyr Leu Glu Ser 
1               5           


<210>  30
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  light chain variable domain of PD-1 mAb 2 CDR3

<400>  30

Gln His Ser Arg Asp Leu Pro Leu Thr 
1               5                   


<210>  31
<211>  121
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(121)
<223>  heavy chain variable domain of PD-1 mAb 3

<400>  31

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


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


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


Gly Tyr Ile Tyr Pro Ser Thr Gly Phe Thr Glu Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Trp Arg Asp Ser Ser Gly Tyr His Ala Met Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Ser Val Thr Val Ser Ser 
        115                 120     


<210>  32
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 3 CDR1

<400>  32

Ser Ser Trp Ile His 
1               5   


<210>  33
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  heavy chain variable domain of PD-1 mAb 3 CDR2

<400>  33

Tyr Ile Tyr Pro Ser Thr Gly Phe Thr Glu Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  34
<211>  13
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(13)
<223>  heavy chain variable domain of PD-1 mAb 3 CDR3

<400>  34

Arg Trp Arg Asp Ser Ser Gly Tyr His Ala Met Asp Tyr 
1               5                   10              


<210>  35
<211>  111
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(111)
<223>  light chain variable domain of PD-1 mAb 3

<400>  35

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


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


Gly Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Phe Gly Ser Asn Leu Glu Ser Gly Ile Pro Ala 
    50                  55                  60                  


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


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


Glu Ile Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110     


<210>  36
<211>  15
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(15)
<223>  light chain variable domain of PD-1 mAb 3 CDR1

<400>  36

Arg Ala Ser Gln Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His 
1               5                   10                  15  


<210>  37
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  light chain variable domain of PD-1 mAb 3 CDR2

<400>  37

Phe Gly Ser Asn Leu Glu Ser 
1               5           


<210>  38
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  light chain variable domain of PD-1 mAb 3 CDR3

<400>  38

Gln His Ser Trp Glu Ile Pro Tyr Thr 
1               5                   


<210>  39
<211>  117
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(117)
<223>  heavy chain variable domain of PD-1 mAb 4

<400>  39

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


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


Gly Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Gln Trp Met 
        35                  40                  45              


Gly Trp Ile Asn Thr Asp Ser Gly Glu Ser Thr Tyr Ala Glu Glu Phe 
    50                  55                  60                  


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


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


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


Val Thr Val Ser Ser 
        115         


<210>  40
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 4 CDR1

<400>  40

Asn Tyr Gly Met Asn 
1               5   


<210>  41
<211>  16
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(16)
<223>  heavy chain variable domain of PD-1 mAb 4 CDR2

<400>  41

Trp Ile Asn Thr Asp Ser Gly Glu Ser Thr Tyr Ala Glu Glu Phe Lys 
1               5                   10                  15      


<210>  42
<211>  8
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)
<223>  heavy chain variable domain of PD-1 mAb 4 CDR3

<400>  42

Val Gly Tyr Asp Ala Leu Asp Tyr 
1               5               


<210>  43
<211>  106
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(106)
<223>  light chain variable domain of PD-1 mAb 4

<400>  43

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


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


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


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


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


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


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


<210>  44
<211>  10
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(10)
<223>  light chain variable domain of PD-1 mAb 4 CDR1

<400>  44

Ser Ala Arg Ser Ser Val Ser Tyr Met His 
1               5                   10  


<210>  45
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  light chain variable domain of PD-1 mAb 4 CDR2

<400>  45

Arg Thr Ser Asn Leu Ala Ser 
1               5           


<210>  46
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  light chain variable domain of PD-1 mAb 4 CDR3

<400>  46

Gln Gln Arg Ser Ser Phe Pro Leu Thr 
1               5                   


<210>  47
<211>  120
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(120)
<223>  Heavy Chain Variable Domain of Murine 4D5 Antibody

<400>  47

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


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


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


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


Gln Asp Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Ala Ser Val Thr Val Ser Ser 
        115                 120 


<210>  48
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain Variable Domain of Humanized 4D5 Antibody

<400>  48

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 Asn Ile Lys Asp Thr 
            20                  25                  30          


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


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


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


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


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


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  49
<211>  217
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(217)
<223>  IgG1 Fc Region

<220>
<221>  MISC_FEATURE
<222>  (217)..(217)
<223>  wherein, X is a lysine (K) or is absent

<400>  49

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


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


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                85                  90                  95      


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


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        115                 120                 125             


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


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


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


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Pro Gly Xaa 
    210                 215         


<210>  50
<211>  216
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(216)
<223>  CH2-CH3 domain of an exemplary human IgG2

<220>
<221>  MISC_FEATURE
<222>  (216)..(216)
<223>  wherein, X is a lysine (K) or is absent

<400>  50

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


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


Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
        35                  40                  45              


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    50                  55                  60                  


Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln 
65                  70                  75                  80  


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
                85                  90                  95      


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
        115                 120                 125             


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


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


Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
                165                 170                 175     


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


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        195                 200                 205             


Ser Leu Ser Leu Ser Pro Gly Xaa 
    210                 215     


<210>  51
<211>  217
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(217)
<223>  CH2-CH3 Domain of an exemplary human IgG3

<220>
<221>  MISC_FEATURE
<222>  (217)..(217)
<223>  wherein, X is a lysine (K) or is absent

<400>  51

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


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


Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                85                  90                  95      


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


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        115                 120                 125             


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


Ser Asp Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


Tyr Asn Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                165                 170                 175     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Pro Gly Xaa 
    210                 215         


<210>  52
<211>  217
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(217)
<223>  CH2-CH3 domain of an exemplary human IgG4

<220>
<221>  MISC_FEATURE
<222>  (217)..(217)
<223>  wherein, X is a lysine (K) or is absent

<400>  52

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


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


Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                85                  90                  95      


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


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met 
        115                 120                 125             


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


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


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


Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Leu Gly Xaa 
    210                 215         


<210>  53
<211>  116
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(116)
<223>  heavy chain variable domain of PD-1 mAb 5

<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 Ser Phe 
            20                  25                  30          


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


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


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


Thr Val Ser Ser 
        115     


<210>  54
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 5 CDR1

<400>  54

Ser Phe Gly Met His 
1               5   


<210>  55
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  heavy chain variable domain of PD-1 mAb 5 CDR2

<400>  55

Tyr Ile Ser Ser Gly Ser Met Ser Ile Ser Tyr Ala Asp Thr Val Lys 
1               5                   10                  15      


Gly 
    


<210>  56
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  heavy chain variable domain of PD-1 mAb 5 CDR3

<400>  56

Leu Ser Asp Tyr Phe Asp Tyr 
1               5           


<210>  57
<211>  112
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(112)
<223>  light chain variable domain of PD-1 mAb 5

<400>  57

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


Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Thr Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


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


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


<210>  58
<211>  16
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(16)
<223>  light chain variable domain of PD-1 mAb 5 CDR1

<400>  58

Arg Ser Ser Gln Ser Leu Val His Ser Thr Gly Asn Thr Tyr Leu His 
1               5                   10                  15      


<210>  59
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  light chain variable domain of PD-1 mAb 5 CDR2

<400>  59

Arg Val Ser Asn Arg Phe Ser 
1               5           


<210>  60
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  light chain variable domain of PD-1 mAb 5 CDR3

<400>  60

Ser Gln Thr Thr His Val Pro Trp Thr 
1               5                   


<210>  61
<211>  119
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(119)
<223>  heavy chain variable domain of PD-1 mAb 6

<400>  61

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


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


Trp Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Xaa 
        35                  40                  45              


Gly Val Ile His Pro Ser Asp Ser Glu Thr Trp Leu Asp Gln Lys Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Ile Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu His Tyr Gly Thr Ser Pro Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  62
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 6 CDR1

<400>  62

Ser Tyr Trp Met Asn 
1               5   


<210>  63
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  heavy chain variable domain of PD-1 mAb 6 CDR2

<400>  63

Val Ile His Pro Ser Asp Ser Glu Thr Trp Leu Asp Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  64
<211>  10
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(10)
<223>  heavy chain variable domain of PD-1 mAb 6 CDR3

<400>  64

Glu His Tyr Gly Thr Ser Pro Phe Ala Tyr 
1               5                   10  


<210>  65
<211>  111
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(111)
<223>  light chain variable domain of PD-1 mAb 6

<400>  65

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Xaa Glu Ser Val Asp Asn Tyr 
            20                  25                  30          


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


Lys Leu Leu Ile His Ala Ala Ser Asn Xaa Gly Ser Gly Val Pro Ser 
    50                  55                  60                  


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


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Ser Lys 
                85                  90                  95      


Glu Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110     


<210>  66
<211>  15
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(15)
<223>  light chain variable domain of PD-1 mAb 6 CDR1

<400>  66

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


<210>  67
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  light chain variable domain of PD-1 mAb 6 CDR2

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  wherein X1 is N or S and X2 is Q or R; or  X1 is N and X2 is Q; 
       or  X1 is S and X2 is Q; or X1 is S and X2 is R

<400>  67

Ala Ala Ser Asn Xaa Gly Ser 
1               5           


<210>  68
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  light chain variable domain of PD-1 mAb 6 CDR3

<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  wherein X1 is N or S and X2 is Q or R; or  X1 is N and X2 is Q; 
       or  X1 is S and X2 is Q; or X1 is S and X2 is R

<400>  68

Gln Gln Ser Lys Glu Val Pro Tyr Thr 
1               5                   


<210>  69
<211>  119
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(119)
<223>  heavy chain variable domain of PD-1 mAb 7

<220>
<221>  MISC_FEATURE
<222>  (1)..(119)
<223>  wherein X1 is V or A; X2 is S or G; X3 is V or T; X4 is L or A; 
       X1 is V, X2 is S, X3 is V, and X4 is L; or X1 is A, X2 is G, X3 
       is T, and X4 is A

<400>  69

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


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


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


Ala Thr Ile Ser Gly Gly Gly Gly Asn Thr Tyr Tyr Ser Asp Ser Val 
    50                  55                  60                  


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  70
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  heavy chain variable domain of PD-1 mAb 7 CDR1

<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  wherein X1 is V or A; X2 is S or G; X3 is V or T; X4 is L or A; 
       X1 is V, X2 is S, X3 is V, and X4 is L; or X1 is A, X2 is G, X3 
       is T, and X4 is A

<400>  70

Ser Tyr Leu Val Xaa 
1               5   


<210>  71
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  heavy chain variable domain of PD-1 mAb 7 CDR2

<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  wherein X1 is V or A; X2 is S or G; X3 is V or T; X4 is L or A; 
       X1 is V, X2 is S, X3 is V, and X4 is L; or X1 is A, X2 is G, X3 
       is T, and X4 is A

<400>  71

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


Gly 
    


<210>  72
<211>  10
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(10)
<223>  heavy chain variable domain of PD-1 mAb 7 CDR3

<220>
<221>  MISC_FEATURE
<222>  (1)..(10)
<223>  wherein X1 is V or A; X2 is S or G; X3 is V or T; X4 is L or A; 
       X1 is V, X2 is S, X3 is V, and X4 is L; or X1 is A, X2 is G, X3 
       is T, and X4 is A

<400>  72

Tyr Gly Phe Asp Gly Ala Trp Phe Ala Tyr 
1               5                   10  


<210>  73
<211>  107
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  light chain variable domain of PD-1 mAb 7

<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  wherein X1 is N or S and X2 is N or D; X1 is S and X2 is N; or X1
       is N and X2 is D

<400>  73

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


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


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


Tyr Xaa Ala Lys Thr Leu Ala Ala 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 His His Tyr Ala Val Pro Trp 
                85                  90                  95      


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


<210>  74
<211>  11
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(11)
<223>  PD-1 mAb 7  CDRL1

<220>
<221>  MISC_FEATURE
<222>  (1)..(11)
<223>  wherein X1 is N or S and X2 is N or D; X1 is S and X2 is N; or X1
       is N and X2 is D

<400>  74

Arg Ala Ser Glu Asn Ile Tyr Xaa Tyr Leu Ala 
1               5                   10      


<210>  75
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  PD-1 mAb 7  CDRL2

<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  wherein X1 is N or S and X2 is N or D; X1 is S and X2 is N; or X1
       is N and X2 is D

<400>  75

Xaa Ala Lys Thr Leu Ala Ala 
1               5           


<210>  76
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  PD-1 mAb 7  CDRL3

<400>  76

Gln His His Tyr Ala Val Pro Trp Thr 
1               5                   


<210>  77
<211>  117
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(117)
<223>  heavy chain variable domain of PD-1 mAb 8

<400>  77

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


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


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


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


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


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


Ala Arg Arg Gly Thr Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  78
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)
<223>  PD-1 mAb 8  CDRH1

<400>  78

Ser Tyr Leu Ile Ser 
1               5   


<210>  79
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  PD-1 mAb 8  CDRH2

<400>  79

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


Gly 
    


<210>  80
<211>  8
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)
<223>  PD-1 mAb 8  CDRH3

<400>  80

Arg Gly Thr Tyr Ala Met Asp Tyr 
1               5               


<210>  81
<211>  107
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  light chain variable domain of PD-1 mAb 8

<400>  81

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


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


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


Tyr Asp Ala Lys Thr Leu Ala Ala 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 His His Tyr Ala Val Pro Trp 
                85                  90                  95      


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


<210>  82
<211>  11
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(11)
<223>  PD-1 mAb 8  CDRL1

<400>  82

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


<210>  83
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)
<223>  PD-1 mAb 8  CDRL2

<400>  83

Asp Ala Lys Thr Leu Ala Ala 
1               5           


<210>  84
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(9)
<223>  PD-1 mAb 8  CDRL3

<400>  84

Gln His His Tyr Ala Val Pro Trp Thr 
1               5                   


<210>  85
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  kappa CL Domain

<400>  85

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>  86
<211>  110
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(110)
<223>  IgG4 CH1 Domain and Stabilized Hinge

<400>  86

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 
            100                 105                 110 


<210>  87
<211>  445
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(445)
<223>  complete heavy chain of PD-1 mAb 6-ISQ

<400>  87

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


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


Trp Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Val Ile His Pro Ser Asp Ser Glu Thr Trp Leu Asp Gln Lys Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Ile Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu His Tyr Gly Thr Ser Pro Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


