                         SEQUENCE LISTING

<110>  MacroGenics, Inc.
       Bonvini, Ezio
       Johnson, Leslie S
       Moore, Paul A
       Shah, Kalpana
       La Motte-Mohs, Ross
 
<120>  Covalently Bonded Diabodies Having Immunoreactivity with PD-1 and
        LAG-3 and Methods of Use Thereof

<130>  1301.0115PCT

<150>  62/017,467
<151>  2014-06-26

<160>  32    

<170>  PatentIn version 3.5

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


<220>
<221>  misc
<222>  (1)..(288)
<223>  human PD-1 including signal sequence

<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>  113
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(113)
<223>  Anti-PD-1 Antibody mAb 1 Heavy Chain Variable Region

<400>  2

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>  3
<211>  107
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(107)
<223>  Anti-PD-1 Antibody mAb 1 Light Chain Variable Region

<400>  3

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>  4
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized Anti-PD-1 Antibody mAb 2 Heavy Chain Variable Region

<400>  4

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>  5
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized Anti-PD-1 Antibody mAb 2 Light Chain Variable Region

<400>  5

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>  6
<211>  121
<212>  PRT
<213>  Mus musculus

<400>  6

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>  7
<211>  111
<212>  PRT
<213>  Mus musculus


<220>
<221>  MISC_FEATURE
<222>  (1)..(111)
<223>  Anti-PD-1 Antibody mAb 3 Light Chain Variable Region

<400>  7

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>  8
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized Anti-PD-1 Antibody mAb 4 Heavy Chain Variable Region

<400>  8

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>  9
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized Anti-PD-1 Antibody mAb 4 Light Chain Variable Region

<400>  9

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>  10
<211>  525
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(525)
<223>  human LAG3 (CD223) protein including signal sequence

<400>  10

Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 
1               5                   10                  15      


Val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val 
            20                  25                  30          


Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 
        35                  40                  45              


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


His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu 
65                  70                  75                  80  


Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 
                85                  90                  95      


Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 
            100                 105                 110         


Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 
        115                 120                 125             


Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 
    130                 135                 140                 


Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 
145                 150                 155                 160 


Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 
                165                 170                 175     


Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 
            180                 185                 190         


Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 
        195                 200                 205             


Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 
    210                 215                 220                 


Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 
225                 230                 235                 240 


Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 
                245                 250                 255     


Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 
            260                 265                 270         


Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 
        275                 280                 285             


Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 
    290                 295                 300                 


Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 
305                 310                 315                 320 


Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 
                325                 330                 335     


Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 
            340                 345                 350         


Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 
        355                 360                 365             


Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 
    370                 375                 380                 


Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 
385                 390                 395                 400 


Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 
                405                 410                 415     


Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 
            420                 425                 430         


Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala Leu Pro Ala Gly 
        435                 440                 445             


His Leu Leu Leu Phe Leu Ile Leu Gly Val Leu Ser Leu Leu Leu Leu 
    450                 455                 460                 


Val Thr Gly Ala Phe Gly Phe His Leu Trp Arg Arg Gln Trp Arg Pro 
465                 470                 475                 480 


Arg Arg Phe Ser Ala Leu Glu Gln Gly Ile His Pro Pro Gln Ala Gln 
                485                 490                 495     


Ser Lys Ile Glu Glu Leu Glu Gln Glu Pro Glu Pro Glu Pro Glu Pro 
            500                 505                 510         


Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Gln Leu 
        515                 520                 525 


<210>  11
<211>  120
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(120)
<223>  Anti-LAG-3 Antibody mAb 1 Heavy Chain Variable Region

<400>  11

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


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


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


Gly Glu Ile Asn His Asn Gly Asn Thr Asn Ser Asn Pro Ser Leu Lys 
    50                  55                  60                  


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


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


Phe Gly Tyr Ser Asp Tyr Glu Tyr Asn Trp Phe Asp Pro Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  12
<211>  107
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MOD_RES
<222>  (1)..(107)
<223>  Anti-LAG-3 Antibody mAb 1 Light Chain Variable Region

<400>  12

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 Ile 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 Arg Ser Asn Trp Pro Leu 
                85                  90                  95      


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


<210>  13
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker 1

<400>  13

Gly Gly Gly Ser Gly Gly Gly Gly 
1               5               


<210>  14
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  E-Coil Heterodimer-Promoting Domain

<400>  14

Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val 
1               5                   10                  15      


Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 
            20                  25              


<210>  15
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  K-Coil Heterodimer-Promoting Domain

<400>  15

Lys Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val 
1               5                   10                  15      


Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 
            20                  25              


<210>  16
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine-Containing E-Coil Heterodimer-Promoting Domain

<400>  16

Glu Val Ala Ala Cys Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val 
1               5                   10                  15      


Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 
            20                  25              


<210>  17
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine-Containing K-Coil Heterodimer-Promoting Domain

<400>  17

Lys Val Ala Ala Cys Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val 
1               5                   10                  15      


Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 
            20                  25              


<210>  18
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine-Containing Spacer Peptide

<400>  18

Gly Gly Cys Gly Gly Gly 
1               5       


<210>  19
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cysteine-Containing Linker Peptide

<400>  19

Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10  


<210>  20
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Alternative Cysteine-Containing Linker Peptide

<400>  20

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


<210>  21
<211>  218
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(218)
<223>  IgG1 Fc Region

<400>  21

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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215             


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

<220>
<223>  "Knob-Bearing" IgG1 CH2-CH3 Domain

<400>  22

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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215             


<210>  23
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  "Hole-Bearing" IgG1 CH2-CH3 Domain

<400>  23

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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215             


<210>  24
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG1 Fc Region L234A/L235A Variant

<400>  24

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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    210                 215         


<210>  25
<211>  494
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  First and Third Polypeptide Chains of the Exemplary PD-1 x LAG-3 
       Fc-DART-1 diabody

<400>  25

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 Ile 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 Arg Ser Asn Trp Pro Leu 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Asn Leu Glu Ile Lys Gly Gly Gly Ser Gly 
            100                 105                 110         


Gly Gly Gly Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 
        115                 120                 125             


Pro Gly Arg Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe 
    130                 135                 140                 


Ser Asn Ser Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
145                 150                 155                 160 


Glu Trp Val Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala 
                165                 170                 175     


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
            180                 185                 190         


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


Tyr Tyr Cys Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val 
    210                 215                 220                 


Thr Val Ser Ser Gly Gly Cys Gly Gly Gly Glu Val Ala Ala Cys Glu 
225                 230                 235                 240 


Lys Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys Glu 
                245                 250                 255     


Val Ala Ala Leu Glu Lys Leu Glu Pro Lys Ser Ala Asp Lys Thr His 
            260                 265                 270         


Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
        275                 280                 285             


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu 
    290                 295                 300                 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
305                 310                 315                 320 


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                325                 330                 335     


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


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
        355                 360                 365             


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
    370                 375                 380                 


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


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
                405                 410                 415     


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
            420                 425                 430         


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
        435                 440                 445             


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
    450                 455                 460                 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
465                 470                 475                 480 


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                485                 490                 


<210>  26
<211>  1482
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding the First and Third Polypeptide Chains of
       the Exemplary PD-1 x LAG-3 Fc-DART-1 diabody

<400>  26
gaaattgtcc tgacacagtc tcccgcaacc ctgagtttga gtcctgggga gcgagcaact       60

ctctcctgcc gagcctccca gagtatctcc tcctacctcg cctggtacca acagaagcca      120

gggcaggctc caaggctgct tatctatgac gcctctaacc gcgcaactgg gattcccgca      180

cgcttctccg gctctggttc cggcacagac tttacactta ctatctctag cctggagcca      240

gaagactttg ccgtgtacta ttgtcagcaa cgttccaatt ggccccttac ctttgggcag      300

ggcactaact tggaaatcaa aggtggcgga tccggcggcg gaggccaggt tcagctggtc      360

gagagtggtg gcggcgttgt gcaacctggg cgttccctcc gattggactg taaagcttcc      420

ggcattactt tctcaaattc cggcatgcat tgggtgaggc aagcccctgg aaaagggctc      480

gaatgggtgg ctgtgatttg gtacgatggc agcaaacggt actacgccga ttctgttaag      540

ggccgcttta ccatctcccg cgataactca aagaacacac tgtttctgca aatgaatagt      600

cttagagccg aggacaccgc cgtgtactac tgtgccacaa atgacgatta ttgggggcag      660

ggcacattgg tcacagtgtc ttccggagga tgtggcggtg gagaagtggc cgcatgtgag      720

aaagaggttg ctgctttgga gaaggaggtc gctgcacttg aaaaggaggt cgcagccctg      780

gagaaactgg agcccaaatc tgctgacaaa actcacacat gcccaccgtg cccagcacct      840

gaagccgcgg ggggaccgtc agtcttcctc ttccccccaa aacccaagga caccctctat      900

atcacccggg agcctgaggt cacatgcgtg gtggtggacg tgagccacga agaccctgag      960

gtcaagttca actggtacgt ggacggcgtg gaggtgcata atgccaagac aaagccgcgg     1020

gaggagcagt acaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac     1080

tggctgaatg gcaaggagta caagtgcaag gtctccaaca aagccctccc agcccccatc     1140

gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta caccctgccc     1200

ccatcccggg aggagatgac caagaaccag gtcagcctga cctgcctggt caaaggcttc     1260

tatcccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag     1320

accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcaa gctcaccgtg     1380

gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgatgca tgaggctctg     1440

cacaaccact acacgcagaa gagcctctcc ctgtctccgg gt                        1482


<210>  27
<211>  269
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Second and Fourth Polypeptide Chains of the Exemplary PD-1 x 
       LAG-3 Fc-DART-1 diabody

<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 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 Gly Gly Gly Ser Gly 
            100                 105                 110         


Gly Gly Gly Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys 
        115                 120                 125             


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


Ser Asp Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 
145                 150                 155                 160 


Glu Trp Ile Gly Glu Ile Asn His Asn Gly Asn Thr Asn Ser Asn Pro 
                165                 170                 175     


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


Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
        195                 200                 205             


Tyr Cys Ala Phe Gly Tyr Ser Asp Tyr Glu Tyr Asn Trp Phe Asp Pro 
    210                 215                 220                 


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Cys Gly Gly 
225                 230                 235                 240 


Gly Lys Val Ala Ala Cys Lys Glu Lys Val Ala Ala Leu Lys Glu Lys 
                245                 250                 255     


Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 
            260                 265                 


<210>  28
<211>  807
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding the Second and Fourth Polypeptide Chains 
       of the Exemplary PD-1 x LAG-3 Fc-DART-1 diabody

<400>  28
gagatcgtac ttacccagtc tcccgccacc ctttccctga gtcctggtga gcgggccact       60

ctttcctgtc gcgcaagcca atcagtttct agctacctcg catggtatca gcagaagcca      120

gggcaggcac ccaggcttct catctatgac gccagtaacc gcgcaaccgg gatacctgct      180

agattttccg gcagtggatc tgggaccgat ttcacactga caatttcatc cttggaacca      240

gaagatttcg cagtctacta ctgccagcaa tcttccaact ggccaagaac tttcggacag      300

gggaccaaag tggaaattaa aggtggcgga tccggcggcg gaggccaggt ccagctccag      360

caatggggag ccgggctgct gaaaccctct gaaacactga gtctcacatg tgccgtttat      420

ggaggttcct tctccgatta ttactggaac tggattcgtc agcctcccgg caagggcctg      480

gagtggatcg gtgagattaa ccacaatggc aataccaata gcaatcctag tttgaaatct      540

cgcgtcactc tttccctcga tacaagcaaa aaccagtttt ctttgaaatt gcgatctgta      600

actgctgctg atactgccgt gtattactgc gcattcggct actccgacta tgaatataat      660

tggttcgatc cttggggaca gggaacattg gtaaccgtgt catccggagg atgtggcggt      720

ggaaaagtgg ccgcatgtaa ggagaaagtt gctgctttga aagagaaggt cgccgcactt      780

aaggaaaagg tcgcagccct gaaagag                                          807


<210>  29
<211>  501
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  First and Third Polypeptide Chains of the Exemplary PD-1 x LAG-3 
       Fc-DART-2 diabody

<400>  29

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 Gly Gly Gly Ser Gly 
            100                 105                 110         


Gly Gly Gly Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys 
        115                 120                 125             


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


Ser Asp Tyr Tyr Trp Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 
145                 150                 155                 160 


Glu Trp Ile Gly Glu Ile Asn His Asn Gly Asn Thr Asn Ser Asn Pro 
                165                 170                 175     


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


Phe Ser Leu Lys Leu Arg Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 
        195                 200                 205             


Tyr Cys Ala Phe Gly Tyr Ser Asp Tyr Glu Tyr Asn Trp Phe Asp Pro 
    210                 215                 220                 


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Cys Gly Gly 
225                 230                 235                 240 


Gly Glu Val Ala Ala Cys Glu Lys Glu Val Ala Ala Leu Glu Lys Glu 
                245                 250                 255     


Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys Leu Glu Pro 
            260                 265                 270         


Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
        275                 280                 285             


Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
    290                 295                 300                 


Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp 
305                 310                 315                 320 


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


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
            340                 345                 350         


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
        355                 360                 365             


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
    370                 375                 380                 


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
385                 390                 395                 400 


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                405                 410                 415     


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
            420                 425                 430         


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
        435                 440                 445             


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
    450                 455                 460                 


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
465                 470                 475                 480 


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                485                 490                 495     


Ser Leu Ser Pro Gly 
            500     


<210>  30
<211>  1503
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding the First and Third Polypeptide Chains of
       the Exemplary PD-1 x LAG-3 Fc-DART-2 diabody

<400>  30
gagatcgtac ttacccagtc tcccgccacc ctttccctga gtcctggtga gcgggccact       60

ctttcctgtc gcgcaagcca atcagtttct agctacctcg catggtatca gcagaagcca      120

gggcaggcac ccaggcttct catctatgac gccagtaacc gcgcaaccgg gatacctgct      180

agattttccg gcagtggatc tgggaccgat ttcacactga caatttcatc cttggaacca      240

gaagatttcg cagtctacta ctgccagcaa tcttccaact ggccaagaac tttcggacag      300

gggaccaaag tggaaattaa aggtggcgga tccggcggcg gaggccaggt ccagctccag      360

caatggggag ccgggctgct gaaaccctct gaaacactga gtctcacatg tgccgtttat      420

ggaggttcct tctccgatta ttactggaac tggattcgtc agcctcccgg caagggcctg      480

gagtggatcg gtgagattaa ccacaatggc aataccaata gcaatcctag tttgaaatct      540

cgcgtcactc tttccctcga tacaagcaaa aaccagtttt ctttgaaatt gcgatctgta      600

actgctgctg atactgccgt gtattactgc gcattcggct actccgacta tgaatataat      660

tggttcgatc cttggggaca gggaacattg gtaaccgtgt catccggagg atgtggcggt      720

ggagaagtgg ccgcatgtga gaaagaggtt gctgctttgg agaaggaggt cgctgcactt      780

gaaaaggagg tcgcagccct ggagaaactg gagcccaaat ctgctgacaa aactcacaca      840

tgcccaccgt gcccagcacc tgaagccgcg gggggaccgt cagtcttcct cttcccccca      900

aaacccaagg acaccctcta tatcacccgg gagcctgagg tcacatgcgt ggtggtggac      960

gtgagccacg aagaccctga ggtcaagttc aactggtacg tggacggcgt ggaggtgcat     1020

aatgccaaga caaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc     1080

ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac     1140

aaagccctcc cagcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa     1200

ccacaggtgt acaccctgcc cccatcccgg gaggagatga ccaagaacca ggtcagcctg     1260

acctgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg     1320

cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc     1380

ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc     1440

tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg     1500

ggt                                                                   1503


<210>  31
<211>  262
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Second and Fourth Polypeptide Chains of the Exemplary PD-1 x 
       LAG-3 Fc-DART-2 diabody

<400>  31

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 Ile 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 Arg Ser Asn Trp Pro Leu 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Asn Leu Glu Ile Lys Gly Gly Gly Ser Gly 
            100                 105                 110         


Gly Gly Gly Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 
        115                 120                 125             


Pro Gly Arg Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe 
    130                 135                 140                 


Ser Asn Ser Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
145                 150                 155                 160 


Glu Trp Val Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala 
                165                 170                 175     


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
            180                 185                 190         


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


Tyr Tyr Cys Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val 
    210                 215                 220                 


Thr Val Ser Ser Gly Gly Cys Gly Gly Gly Lys Val Ala Ala Cys Lys 
225                 230                 235                 240 


Glu Lys Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu Lys 
                245                 250                 255     


Val Ala Ala Leu Lys Glu 
            260         


<210>  32
<211>  786
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucleotide Encoding the Second and Fourth Polypeptide Chains 
       of the Exemplary PD-1 x LAG-3 Fc-DART-2 diabody

<400>  32
gaaattgtcc tgacacagtc tcccgcaacc ctgagtttga gtcctgggga gcgagcaact       60

ctctcctgcc gagcctccca gagtatctcc tcctacctcg cctggtacca acagaagcca      120

gggcaggctc caaggctgct tatctatgac gcctctaacc gcgcaactgg gattcccgca      180

cgcttctccg gctctggttc cggcacagac tttacactta ctatctctag cctggagcca      240

gaagactttg ccgtgtacta ttgtcagcaa cgttccaatt ggccccttac ctttgggcag      300

ggcactaact tggaaatcaa aggtggcgga tccggcggcg gaggccaggt tcagctggtc      360

gagagtggtg gcggcgttgt gcaacctggg cgttccctcc gattggactg taaagcttcc      420

ggcattactt tctcaaattc cggcatgcat tgggtgaggc aagcccctgg aaaagggctc      480

gaatgggtgg ctgtgatttg gtacgatggc agcaaacggt actacgccga ttctgttaag      540

ggccgcttta ccatctcccg cgataactca aagaacacac tgtttctgca aatgaatagt      600

cttagagccg aggacaccgc cgtgtactac tgtgccacaa atgacgatta ttgggggcag      660

ggcacattgg tcacagtgtc ttccggagga tgtggcggtg gaaaagtggc cgcatgtaag      720

gagaaagttg ctgctttgaa agagaaggtc gccgcactta aggaaaaggt cgcagccctg      780

aaagag                                                                 786


