                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Bispecific Antibodies specifically binding to PD1 and LAG3

<130>  P34215-WO

<150>  EP17165125.0
<151>  2017-04-05

<160>  169   

<170>  PatentIn version 3.5

<210>  1
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, PD1-0103

<400>  1

Gly Phe Ser Phe Ser Ser Tyr 
1               5           


<210>  2
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, PD1-0103

<400>  2

Gly Gly Arg 
1           


<210>  3
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, PD1-0103

<400>  3

Thr Gly Arg Val Tyr Phe Ala Leu Asp 
1               5                   


<210>  4
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, PD1-0103

<400>  4

Ser Glu Ser Val Asp Thr Ser Asp Asn Ser Phe 
1               5                   10      


<210>  5
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, PD1-0103

<400>  5

Arg Ser Ser 
1           


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

<220>
<223>  light chain HVR-L3, PD1-0103

<400>  6

Asn Tyr Asp Val Pro Trp 
1               5       


<210>  7
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, PD1-0103

<400>  7

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


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


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


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


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


Gly Thr Ser Val Thr Val Ser Ser 
        115                 120 


<210>  8
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, PD1-0103

<400>  8

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


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


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro 
        35                  40                  45              


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


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


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


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


<210>  9
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized variant -heavy chain variable domain VH of PD1-0103_01 
       (PD1 0376)

<400>  9

Glu Val Gln Leu Leu 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 Ser Phe Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  10
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized variant -light chain variable domain VL of PD1-0103_01 
       (PD1 0376)

<400>  10

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


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


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 
        35                  40                  45              


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


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


<210>  11
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized variant -light chain variable domain VL of PD1-0103_02

<400>  11

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 Ala Ser Glu Ser Val Asp Thr Ser 
            20                  25                  30          


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro 
        35                  40                  45              


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


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


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


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


<210>  12
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized variant -light chain variable domain VL of PD1-0103_03

<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 Glu Ser Val Asp Thr Ser 
            20                  25                  30          


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Ile 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 Gln Asn Tyr 
                85                  90                  95      


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


<210>  13
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized variant -light chain variable domain VL of PD1-0103_04

<400>  13

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 Glu Ser Val Asp Thr Ser 
            20                  25                  30          


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu Ser Gly Ile 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 Gln Asn Tyr 
                85                  90                  95      


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


<210>  14
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, aLAG3(0414)

<400>  14

Asp Tyr Thr Met Asn 
1               5   


<210>  15
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, aLAG3(0414)

<400>  15

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


Gly 
    


<210>  16
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, aLAG3(0414)

<400>  16

Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr 
1               5                   10          


<210>  17
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, aLAG3(0414)

<400>  17

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


<210>  18
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, aLAG3(0414)

<400>  18

Ala Ala Ser Thr Leu Gln Ser 
1               5           


<210>  19
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, aLAG3(0414)

<400>  19

Gln Gln Thr Tyr Ser Ser Pro Leu Thr 
1               5                   


<210>  20
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, aLAG3(0414)

<400>  20

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  21
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, aLAG3(0414)

<400>  21

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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


<210>  22
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, aLAG3(0403)

<400>  22

Asp Tyr Thr Met His 
1               5   


<210>  23
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, aLAG3(0403)

<400>  23

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


Gly 
    


<210>  24
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, aLAG3(0403)

<400>  24

Ala Ile Thr Asp Thr Ser Leu Tyr Gly Tyr Asp Tyr 
1               5                   10          


<210>  25
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, aLAG3(0403)

<400>  25

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


<210>  26
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, aLAG3(0403)

<400>  26

Ala Ala Ser Ser Leu Gln Ser 
1               5           


<210>  27
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, aLAG3(0403)

<400>  27

Gln Gln Thr Tyr Ser Thr Pro Leu Thr 
1               5                   


<210>  28
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, aLAG3(0403)

<400>  28

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


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


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


Ser Leu Val Ser Trp Asp Gly Gly Gly Thr Tyr Tyr Thr Asn Ser Val 
    50                  55                  60                  


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


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


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


Gln Gly Ile Leu Val Thr Val Ser Ser 
        115                 120     


<210>  29
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, aLAG3(0403)

<400>  29

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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


<210>  30
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, aLAG3(0411)

<400>  30

Asp Tyr Thr Met Asn 
1               5   


<210>  31
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, aLAG3(0411)

<400>  31

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


Gly 
    


<210>  32
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, aLAG3(0411)

<400>  32

Gly Leu Thr Asp Asp Thr Leu Tyr Gly Ser Asp Tyr 
1               5                   10          


<210>  33
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, aLAG3(0411)

<400>  33

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


<210>  34
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, aLAG3(0411)

<400>  34

Ala Ser Ser Ser Leu Gln Ser 
1               5           


<210>  35
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, aLAG3(0411)

<400>  35

Gln Gln Thr Tyr Ser Thr Pro Leu Thr 
1               5                   


<210>  36
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, aLAG3(0411)

<400>  36

Glu Val His Leu Leu 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 Ile Val Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Asp Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


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

<220>
<223>  light chain variable domain VL, aLAG3(0411)

<400>  37

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 Ser Ile Val Ser Tyr 
            20                  25                  30          


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


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


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


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


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


<210>  38
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, aLAG3(0417)

<400>  38

Asp Tyr Ala Met Ser 
1               5   


<210>  39
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, aLAG3(0417)

<400>  39

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


Gly 
    


<210>  40
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, aLAG3(0417)

<400>  40

Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile 
1               5                   10              


<210>  41
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, aLAG3(0417)

<400>  41

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


<210>  42
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, aLAG3(0417)

<400>  42

Ala Ala Ser Ser Leu Gln Ser 
1               5           


<210>  43
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, aLAG3(0417)

<400>  43

Gln Gln Thr Tyr Ser Thr Pro Leu Thr 
1               5                   


<210>  44
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, aLAG3(0417)

<400>  44

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


Gly Gln Gly Thr Met Val Thr Val Ser Ser 
        115                 120         


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

<220>
<223>  light chain variable domain VL, aLAG3(0417)

<400>  45

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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


<210>  46
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, aLAG3(0416)

<400>  46

Asp Tyr Ala Met Ser 
1               5   


<210>  47
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, aLAG3(0416)

<400>  47

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


Gly 
    


<210>  48
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, aLAG3(0416)

<400>  48

Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile 
1               5                   10              


<210>  49
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, aLAG3(0416)

<400>  49

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


<210>  50
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, aLAG3(0416)

<400>  50

Asp Ala Ser Ser Leu Glu Ser 
1               5           


<210>  51
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, aLAG3(0416)

<400>  51

Gln Gln Ser Tyr Ser Thr Pro Leu Thr 
1               5                   


<210>  52
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, aLAG3(0416)

<400>  52

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


Gly Gln Gly Thr Met Val Thr Val Ser Ser 
        115                 120         


<210>  53
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, aLAG3(0416)

<400>  53

Asp Ile Gln Leu 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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


<210>  54
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, BMS-986016

<400>  54

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 Arg Gly Ser 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>  55
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL BMS-986016

<400>  55

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>  56
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, MDX25F7 (25F7)

<400>  56

Asp Tyr Tyr Trp Asn 
1               5   


<210>  57
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, MDX25F7 (25F7)

<400>  57

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


<210>  58
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, MDX25F7 (25F7)

<400>  58

Gly Tyr Ser Asp Tyr Glu Tyr Asn Trp Phe 
1               5                   10  


<210>  59
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, MDX25F7 (25F7)

<400>  59

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


<210>  60
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, MDX25F7 (25F7)

<400>  60

Asp Ala Ser Asn Arg Ala Thr 
1               5           


<210>  61
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, MDX25F7 (25F7)

<400>  61

Gln Gln Arg Ser Asn Trp Pro Leu Thr 
1               5                   


<210>  62
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, MDX25F7 (25F7)

<400>  62

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>  63
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, MDX25F7 (25F7)

<400>  63

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>  64
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, humanized BAP050 (LAG525)

<400>  64

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


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


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


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


Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Ser 
65                  70                  75                  80  


Leu Gln Ile Asn Asn Leu Lys Asn Ala Asp Thr Ala Thr Tyr Phe Cys 
                85                  90                  95      


Ala Arg Asn Pro Pro Tyr Tyr Tyr Gly Thr Asn Asn Ala Glu Ala Met 
            100                 105                 110         


Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 125 


<210>  65
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, humanized BAP050 (LAG525)

<400>  65

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


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


Leu Met Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Val Leu Ile 
        35                  40                  45              


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


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Leu 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Asn Leu Pro Trp 
                85                  90                  95      


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


<210>  66
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, MDX26H10 (26H10)

<400>  66

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


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


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


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


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


Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120         


<210>  67
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, MDX26H10 (26H10)

<400>  67

Glu Ile Val Leu Thr Gln Ser Pro Gly 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 Ser 
            20                  25                  30          


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


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


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


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


Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys 
            100                 105             


<210>  68
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human kappa light chain constant region

<400>  68

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>  69
<211>  105
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human lambda light chain constant region

<400>  69

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


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


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


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


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


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


Lys Thr Val Ala Pro Thr Glu Cys Ser 
            100                 105 


<210>  70
<211>  329
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human heavy chain constant region derived from IgG1

<400>  70

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


Ser Thr Ser Gly Gly 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 Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
225                 230                 235                 240 


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                325                 


<210>  71
<211>  329
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human heavy chain constant region derived from IgG1 with 
       mutations L234A, L235A and P329G

<400>  71

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


Ser Thr Ser Gly Gly 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 Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
225                 230                 235                 240 


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                325                 


<210>  72
<211>  326
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human heavy chain constant region derived from IgG4

<400>  72

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser Leu Ser Leu Gly 
                325     


<210>  73
<211>  497
<212>  PRT
<213>  Homo sapiens

<400>  73

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


Ser Pro Thr Ile Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly 
            20                  25                  30          


Val Thr Trp Gln His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro 
        35                  40                  45              


Gly His Pro Leu Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp 
    50                  55                  60                  


Gly Pro Arg Pro Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly 
65                  70                  75                  80  


Leu Arg Ser Gly Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu 
                85                  90                  95      


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


Arg Ala Asp Ala Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg 
        115                 120                 125             


Ala Leu Ser Cys Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr 
    130                 135                 140                 


Ala Ser Pro Pro Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn 
145                 150                 155                 160 


Cys Ser Phe Ser Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg 
                165                 170                 175     


Asn Arg Gly Gln Gly Arg Val Pro Val Arg Glu Ser Pro His His His 
            180                 185                 190         


Leu Ala Glu Ser Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser 
        195                 200                 205             


Gly Pro Trp Gly Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser 
    210                 215                 220                 


Ile Met Tyr Asn Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu 
225                 230                 235                 240 


Thr Val Tyr Ala Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu 
                245                 250                 255     


Pro Ala Gly Val Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro 
            260                 265                 270         


Pro Gly Gly Gly Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe 
        275                 280                 285             


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


Cys His Ile His Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu 
305                 310                 315                 320 


Ala Ile Ile Thr Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu 
                325                 330                 335     


Gly Lys Leu Leu Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe 
            340                 345                 350         


Val Trp Ser Ser Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro 
        355                 360                 365             


Trp Leu Glu Ala Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys 
    370                 375                 380                 


Gln Leu Tyr Gln Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr 
385                 390                 395                 400 


Glu Leu Ser Ser Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala 
                405                 410                 415     


Leu Pro Ala Gly His Leu Leu Leu Phe Leu Ile Leu Gly Val Leu Ser 
            420                 425                 430         


Leu Leu Leu Leu Val Thr Gly Ala Phe Gly Phe His Leu Trp Arg Arg 
        435                 440                 445             


Gln Trp Arg Pro Arg Arg Phe Ser Ala Leu Glu Gln Gly Ile His Pro 
    450                 455                 460                 


Pro Gln Ala Gln Ser Lys Ile Glu Glu Leu Glu Gln Glu Pro Glu Pro 
465                 470                 475                 480 


Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Gln 
                485                 490                 495     


Leu 
    


<210>  74
<211>  422
<212>  PRT
<213>  Homo sapiens

<400>  74

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


Ser Pro Thr Ile Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly 
            20                  25                  30          


Val Thr Trp Gln His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro 
        35                  40                  45              


Gly His Pro Leu Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp 
    50                  55                  60                  


Gly Pro Arg Pro Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly 
65                  70                  75                  80  


Leu Arg Ser Gly Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu 
                85                  90                  95      


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


Arg Ala Asp Ala Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg 
        115                 120                 125             


Ala Leu Ser Cys Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr 
    130                 135                 140                 


Ala Ser Pro Pro Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn 
145                 150                 155                 160 


Cys Ser Phe Ser Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg 
                165                 170                 175     


Asn Arg Gly Gln Gly Arg Val Pro Val Arg Glu Ser Pro His His His 
            180                 185                 190         


Leu Ala Glu Ser Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser 
        195                 200                 205             


Gly Pro Trp Gly Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser 
    210                 215                 220                 


Ile Met Tyr Asn Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu 
225                 230                 235                 240 


Thr Val Tyr Ala Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu 
                245                 250                 255     


Pro Ala Gly Val Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro 
            260                 265                 270         


Pro Gly Gly Gly Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe 
        275                 280                 285             


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


Cys His Ile His Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu 
305                 310                 315                 320 


Ala Ile Ile Thr Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu 
                325                 330                 335     


Gly Lys Leu Leu Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe 
            340                 345                 350         


Val Trp Ser Ser Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro 
        355                 360                 365             


Trp Leu Glu Ala Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys 
    370                 375                 380                 


Gln Leu Tyr Gln Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr 
385                 390                 395                 400 


Glu Leu Ser Ser Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala 
                405                 410                 415     


Leu Pro Ala Gly His Leu 
            420         


<210>  75
<211>  6
<212>  PRT
<213>  Homo sapiens

<400>  75

Lys Ile Glu Glu Leu Glu 
1               5       


<210>  76
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer rbHC.up

<400>  76
aagcttgcca ccatggagac tgggctgcgc tggcttc                                37


<210>  77
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer rbHCf.do

<400>  77
ccattggtga gggtgcccga g                                                 21


<210>  78
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer BcPCR_FHLC_leader.fw

<400>  78
atggacatga gggtccccgc                                                   20


<210>  79
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer BcPCR_huCkappa.rev

<400>  79
gatttcaact gctcatcaga tggc                                              24


<210>  80
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, PD1-0098

<400>  80

Gly Tyr Ser Ile Thr Ser Asp Tyr 
1               5               


<210>  81
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, PD1-0098

<400>  81

Tyr Ser Gly 
1           


<210>  82
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, PD1-0098

<400>  82

His Gly Ser Ala Pro Trp Tyr Phe Asp 
1               5                   


<210>  83
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, PD1-0098

<400>  83

Ser Gln Asn Ile Val His Ser Asp Gly Asn Thr Tyr 
1               5                   10          


<210>  84
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, PD1-0098

<400>  84

Lys Val Ser 
1           


<210>  85
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, PD1-0098

<400>  85

Gly Ser His Phe Pro Leu 
1               5       


<210>  86
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, PD1-0098

<400>  86

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


Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Ser Asp 
            20                  25                  30          


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


Leu Gly Tyr Ile Thr Tyr Ser Gly Phe Thr Asn Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Trp His Gly Ser Ala Pro Trp Tyr Phe Asp Tyr Trp Gly Arg 
            100                 105                 110         


Gly Thr Thr Leu Thr Val Ser Ser 
        115                 120 


<210>  87
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, PD1-0098

<400>  87

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


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


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


Pro Asn Leu Leu Ile Tyr Lys Val Ser Arg 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 Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105                 110         


<210>  88
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H1, PD1-0069

<400>  88

Gly Tyr Thr Phe Thr Asp Tyr 
1               5           


<210>  89
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H2, PD1-0069

<400>  89

Tyr Ser Gly 
1           


<210>  90
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain HVR-H3, PD1-0069

<400>  90

Gly Ile Thr Thr Gly Phe Ala 
1               5           


<210>  91
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L1, PD1-0069

<400>  91

Ser Lys Gly Val Ser Thr Ser Ser Tyr Ser Phe 
1               5                   10      


<210>  92
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L2, PD1-0069

<400>  92

Tyr Ala Ser 
1           


<210>  93
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain HVR-L3, PD1-0069

<400>  93

Ser Arg Glu Phe Pro Trp 
1               5       


<210>  94
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, PD1-0069

<400>  94

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


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


Ala Met His Trp Val Lys Gln Ser His Ala Arg Thr Leu Glu Trp Ile 
        35                  40                  45              


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


Lys Asp Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Leu Val Thr Val Ser Ala 
        115             


<210>  95
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain VL, PD1-0069

<400>  95

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


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


Ser Tyr Ser Phe Met His Trp Tyr Gln Gln Lys Pro Arg Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr 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 Asn Ile His 
65                  70                  75                  80  


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


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


<210>  96
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1 of 1+1 PD1/LAG3 0799

<400>  96

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


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


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 
        35                  40                  45              


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


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


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


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


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


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


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


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


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


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


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


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


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


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp 
            340                 345                 350         


Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 
        355                 360                 365             


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


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


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


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


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440             


<210>  97
<211>  452
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 1+1 PD1/LAG3 0799

<400>  97

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


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


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


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


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
    450         


<210>  98
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 1 of 1+1 PD1/LAG3 0799

<400>  98

Glu Val Gln Leu Leu 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 Ser Phe Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


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


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


Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 
    130                 135                 140                 


Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 
145                 150                 155                 160 


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


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


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


Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 
    210                 215                 220                 


Gly Glu Cys 
225         


<210>  99
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 2 of 1+1 PD1/LAG3 0799

<400>  99

Asp Ile Gln Leu 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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 
                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 Arg Lys 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>  100
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 1+1 PD1/LAG3 0927

<400>  100

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  101
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 2 of 1+1 PD1/LAG3 0927

<400>  101

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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Thr Tyr Ser Ser Pro Leu 
                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 Arg Lys 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>  102
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1 of 1+1 PD1/LAG3 0222

<400>  102

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


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


Ser Tyr Ser Phe Met His Trp Tyr Gln Gln Lys Pro Arg Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr 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 Asn Ile His 
65                  70                  75                  80  


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


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


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


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


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


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


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


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


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


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


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


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


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


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp 
            340                 345                 350         


Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 
        355                 360                 365             


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


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


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


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


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440             


<210>  103
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 1+1 PD1/LAG3 0222

<400>  103

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 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 Glu 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 Glu Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly Ala Pro Ile Glu 
                325                 330                 335     


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


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


Ser Cys Ala 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 Val 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>  104
<211>  225
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 1 of 1+1 PD1/LAG3 0222

<400>  104

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


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


Ala Met His Trp Val Lys Gln Ser His Ala Arg Thr Leu Glu Trp Ile 
        35                  40                  45              


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


Lys Asp Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Leu Val Thr Val Ser Ala Ala Ser Val Ala Ala Pro Ser Val Phe Ile 
        115                 120                 125             


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


Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 
145                 150                 155                 160 


Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 
                165                 170                 175     


Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 
            180                 185                 190         


Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 
        195                 200                 205             


His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 
    210                 215                 220                 


Cys 
225 


<210>  105
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 2 of 1+1 PD1/LAG3 0222

<400>  105

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 Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg Lys 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>  106
<211>  444
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1 of 1+1 PD1/LAG3 0224

<400>  106

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


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


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


Pro Asn Leu Leu Ile Tyr Lys Val Ser Arg 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 Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Phe Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105                 110         


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


Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 
    130                 135                 140                 


Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 
145                 150                 155                 160 


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


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


Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 
        195                 200                 205             


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


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


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


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
            260                 265                 270         


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


Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
    290                 295                 300                 


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


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


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


Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 
        355                 360                 365             


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


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


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


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


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 


<210>  107
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 1 of 1+1 PD1/LAG3 0224

<400>  107

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


Ser Leu Ser Leu Thr Cys Thr Val Thr Gly Tyr Ser Ile Thr Ser Asp 
            20                  25                  30          


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


Leu Gly Tyr Ile Thr Tyr Ser Gly Phe Thr Asn Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Trp His Gly Ser Ala Pro Trp Tyr Phe Asp Tyr Trp Gly Arg 
            100                 105                 110         


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


Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 
    130                 135                 140                 


Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 
145                 150                 155                 160 


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


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


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


Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 
    210                 215                 220                 


Gly Glu Cys 
225         


<210>  108
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0156) heavy chain (MDX25F7)

<400>  108

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 Gly Gln Pro Lys Ala Pro Ser Val 
        115                 120                 125             


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


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


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


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


Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn 
        195                 200                 205             


Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Thr 
    210                 215                 220                 


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


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


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


Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg 
        275                 280                 285             


Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile 
    290                 295                 300                 


Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His 
305                 310                 315                 320 


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg 
                325                 330                 335     


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


Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe 
        355                 360                 365             


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


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


Phe Leu Tyr Asn Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly 
                405                 410                 415     


Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys 
        435                 440             


<210>  109
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0156) light chain (MDX25F7)

<400>  109

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 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>  110
<211>  444
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0414) heavy chain

<400>  110

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val 
            180                 185                 190         


Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro 
    210                 215                 220                 


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


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


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


Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu 
        275                 280                 285             


Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro 
    290                 295                 300                 


Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val 
305                 310                 315                 320 


His Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
                325                 330                 335     


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


Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly 
        355                 360                 365             


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


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


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


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


Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys 
        435                 440                 


<210>  111
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0414) light chain

<400>  111

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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 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>  112
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0416) heavy chain

<400>  112

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


Ser Val Arg Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser 
            180                 185                 190         


Val Thr Ser Ser Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala 
        195                 200                 205             


Thr Asn Thr Lys Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys 
    210                 215                 220                 


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


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


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


Phe Thr Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro 
        275                 280                 285             


Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu 
    290                 295                 300                 


Pro Ile Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys 
305                 310                 315                 320 


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


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


Arg Glu Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn 
        355                 360                 365             


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


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


Ser Tyr Phe Leu Tyr Asn Lys Leu Ser Val Pro Thr Ser Glu Trp Gln 
                405                 410                 415     


Arg Gly Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn 
            420                 425                 430         


His Tyr Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys 
        435                 440                 445 


<210>  113
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  aLAG3(0416) light chain

<400>  113

Asp Ile Gln Leu 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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 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>  114
<211>  695
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of 2+2 PD1/LAG3 8970

<400>  114

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    450                 455                 460                 


Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 
465                 470                 475                 480 


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser 
                485                 490                 495     


Phe Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
            500                 505                 510         


Leu Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr 
        515                 520                 525             


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
    530                 535                 540                 


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
545                 550                 555                 560 


Val Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp 
                565                 570                 575     


Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala 
            580                 585                 590         


Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        595                 600                 605             


Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    610                 615                 620                 


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
625                 630                 635                 640 


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                645                 650                 655     


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            660                 665                 670         


Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        675                 680                 685             


Ser Phe Asn Arg Gly Glu Cys 
    690                 695 


<210>  115
<211>  216
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain 1 of 2+2 PD1/LAG3 8970

<400>  115

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


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


Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro 
        35                  40                  45              


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


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


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


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


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


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


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


Lys Lys Val Glu Pro Lys Ser Cys 
    210                 215     


<210>  116
<211>  696
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of 2+2 PD1/LAG3 8984

<400>  116

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


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


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


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


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu 
465                 470                 475                 480 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                485                 490                 495     


Ser Phe Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
            500                 505                 510         


Gly Leu Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr 
        515                 520                 525             


Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    530                 535                 540                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
545                 550                 555                 560 


Ala Val Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu 
                565                 570                 575     


Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val 
            580                 585                 590         


Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys 
        595                 600                 605             


Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg 
    610                 615                 620                 


Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn 
625                 630                 635                 640 


Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser 
                645                 650                 655     


Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys 
            660                 665                 670         


Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr 
        675                 680                 685             


Lys Ser Phe Asn Arg Gly Glu Cys 
    690                 695     


<210>  117
<211>  694
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of 2+2 PD1/LAG3 9010

<400>  117

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 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 Glu 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 Glu Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly 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 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
    450                 455                 460                 


Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 
465                 470                 475                 480 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe 
                485                 490                 495     


Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            500                 505                 510         


Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro 
        515                 520                 525             


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
    530                 535                 540                 


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
545                 550                 555                 560 


Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser 
                565                 570                 575     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala Ala 
            580                 585                 590         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        595                 600                 605             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    610                 615                 620                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
625                 630                 635                 640 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                645                 650                 655     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            660                 665                 670         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        675                 680                 685             


Phe Asn Arg Gly Glu Cys 
    690                 


<210>  118
<211>  695
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 8310

<400>  118

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    450                 455                 460                 


Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 
465                 470                 475                 480 


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser 
                485                 490                 495     


Phe Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
            500                 505                 510         


Leu Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr 
        515                 520                 525             


Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
    530                 535                 540                 


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
545                 550                 555                 560 


Val Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp 
                565                 570                 575     


Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala 
            580                 585                 590         


Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        595                 600                 605             


Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    610                 615                 620                 


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
625                 630                 635                 640 


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                645                 650                 655     


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            660                 665                 670         


Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        675                 680                 685             


Ser Phe Asn Arg Gly Glu Cys 
    690                 695 


<210>  119
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 2+1 PD1/LAG3 8310

<400>  119

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  120
<211>  696
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 8311

<400>  120

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


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


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


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


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu 
465                 470                 475                 480 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                485                 490                 495     


Ser Phe Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
            500                 505                 510         


Gly Leu Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr 
        515                 520                 525             


Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    530                 535                 540                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
545                 550                 555                 560 


Ala Val Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu 
                565                 570                 575     


Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val 
            580                 585                 590         


Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys 
        595                 600                 605             


Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg 
    610                 615                 620                 


Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn 
625                 630                 635                 640 


Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser 
                645                 650                 655     


Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys 
            660                 665                 670         


Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr 
        675                 680                 685             


Lys Ser Phe Asn Arg Gly Glu Cys 
    690                 695     


<210>  121
<211>  452
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2of 2+1 PD1/LAG3 8311

<400>  121

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


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


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


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


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
    450         


<210>  122
<211>  694
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 1252

<400>  122

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 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 Glu 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 Glu Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly 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 Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp 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 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
    450                 455                 460                 


Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 
465                 470                 475                 480 


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe 
                485                 490                 495     


Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
            500                 505                 510         


Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro 
        515                 520                 525             


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
    530                 535                 540                 


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
545                 550                 555                 560 


Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser 
                565                 570                 575     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala Ala 
            580                 585                 590         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        595                 600                 605             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    610                 615                 620                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
625                 630                 635                 640 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                645                 650                 655     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            660                 665                 670         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        675                 680                 685             


Phe Asn Arg Gly Glu Cys 
    690                 


<210>  123
<211>  941
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 8312

<400>  123

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
    450                 455                 460                 


Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser 
465                 470                 475                 480 


Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser 
                485                 490                 495     


Glu Ser Val Asp Thr Ser Asp Asn Ser Phe Ile His Trp Tyr Gln Gln 
            500                 505                 510         


Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu 
        515                 520                 525             


Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
    530                 535                 540                 


Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr 
545                 550                 555                 560 


Tyr Cys Gln Gln Asn Tyr Asp Val Pro Trp Thr Phe Gly Gln Gly Thr 
                565                 570                 575     


Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 
            580                 585                 590         


Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 
        595                 600                 605             


Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 
    610                 615                 620                 


Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 
625                 630                 635                 640 


Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 
                645                 650                 655     


Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 
            660                 665                 670         


Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
        675                 680                 685             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    690                 695                 700                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
705                 710                 715                 720 


Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
                725                 730                 735     


Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr Thr Met 
            740                 745                 750         


Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Thr 
        755                 760                 765             


Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val Lys Gly 
    770                 775                 780                 


Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 
785                 790                 795                 800 


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val Leu 
                805                 810                 815     


Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln Gly Thr 
            820                 825                 830         


Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        835                 840                 845             


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    850                 855                 860                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
865                 870                 875                 880 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                885                 890                 895     


Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
            900                 905                 910         


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        915                 920                 925             


Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 
    930                 935                 940     


<210>  124
<211>  942
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 8313

<400>  124

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


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


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


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


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


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


Thr Lys Thr His Ser Gly Leu Ile Val Asn Asp Ala Phe Asp Ile Trp 
            100                 105                 110         


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


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


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


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


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


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


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


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
    450                 455                 460                 


Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Asp 
465                 470                 475                 480 


Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ala 
                485                 490                 495     


Ser Glu Ser Val Asp Thr Ser Asp Asn Ser Phe Ile His Trp Tyr Gln 
            500                 505                 510         


Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Arg Ser Ser Thr 
        515                 520                 525             


Leu Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 
    530                 535                 540                 


Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val 
545                 550                 555                 560 


Tyr Tyr Cys Gln Gln Asn Tyr Asp Val Pro Trp Thr Phe Gly Gln Gly 
                565                 570                 575     


Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 
            580                 585                 590         


Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val 
        595                 600                 605             


Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys 
    610                 615                 620                 


Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu 
625                 630                 635                 640 


Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu 
                645                 650                 655     


Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr 
            660                 665                 670         


His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu 
        675                 680                 685             


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    690                 695                 700                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
705                 710                 715                 720 


Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 
                725                 730                 735     


Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr Thr 
            740                 745                 750         


Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 
        755                 760                 765             


Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val Lys 
    770                 775                 780                 


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
785                 790                 795                 800 


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val 
                805                 810                 815     


Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln Gly 
            820                 825                 830         


Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        835                 840                 845             


Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    850                 855                 860                 


Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
865                 870                 875                 880 


Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                885                 890                 895     


Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            900                 905                 910         


Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        915                 920                 925             


Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 
    930                 935                 940         


<210>  125
<211>  940
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 1088

<400>  125

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 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 Glu 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 Glu Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly 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 Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp 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 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu 
465                 470                 475                 480 


Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser Glu 
                485                 490                 495     


Ser Val Asp Thr Ser Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys 
            500                 505                 510         


Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu 
        515                 520                 525             


Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
    530                 535                 540                 


Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr 
545                 550                 555                 560 


Cys Gln Gln Asn Tyr Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys 
                565                 570                 575     


Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 
            580                 585                 590         


Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 
        595                 600                 605             


Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 
    610                 615                 620                 


Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 
625                 630                 635                 640 


Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 
                645                 650                 655     


Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 
            660                 665                 670         


Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly 
        675                 680                 685             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
    690                 695                 700                 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln 
705                 710                 715                 720 


Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
                725                 730                 735     


Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr Thr Met Ser 
            740                 745                 750         


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Thr Ile 
        755                 760                 765             


Ser Gly Gly Gly Arg Asp Ile Tyr Tyr Pro Asp Ser Val Lys Gly Arg 
    770                 775                 780                 


Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met 
785                 790                 795                 800 


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val Leu Leu 
                805                 810                 815     


Thr Gly Arg Val Tyr Phe Ala Leu Asp Ser Trp Gly Gln Gly Thr Leu 
            820                 825                 830         


Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        835                 840                 845             


Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    850                 855                 860                 


Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
865                 870                 875                 880 


Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                885                 890                 895     


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            900                 905                 910         


Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        915                 920                 925             


Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 
    930                 935                 940 


<210>  126
<211>  589
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 1of 2+1 PD1/LAG3 0918

<400>  126

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 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 Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly Ala Pro Ile Glu 
                325                 330                 335     


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


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


Ser Cys Ala 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 Val 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 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu 
465                 470                 475                 480 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                485                 490                 495     


Ser Phe Ser Ser Tyr Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
            500                 505                 510         


Gly Leu Glu Trp Val Ala Thr Ile Ser Gly Gly Gly Arg Asp Ile Tyr 
        515                 520                 525             


Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    530                 535                 540                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
545                 550                 555                 560 


Ala Val Tyr Tyr Cys Val Leu Leu Thr Gly Arg Val Tyr Phe Ala Leu 
                565                 570                 575     


Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            580                 585                 


<210>  127
<211>  580
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 2+1 PD1/LAG3 0918

<400>  127

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 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 Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 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 Gly 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 Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp 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 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu 
465                 470                 475                 480 


Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser Glu 
                485                 490                 495     


Ser Val Asp Thr Ser Asp Asn Ser Phe Ile His Trp Tyr Gln Gln Lys 
            500                 505                 510         


Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Arg Ser Ser Thr Leu Glu 
        515                 520                 525             


Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
    530                 535                 540                 


Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr 
545                 550                 555                 560 


Cys Gln Gln Asn Tyr Asp Val Pro Trp Thr Phe Gly Gln Gly Thr Lys 
                565                 570                 575     


Val Glu Ile Lys 
            580 


<210>  128
<211>  288
<212>  PRT
<213>  Homo sapiens

<400>  128

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>  129
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker G4S

<400>  129

Gly Gly Gly Gly Ser 
1               5   


<210>  130
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker (G4S)2

<400>  130

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  


<210>  131
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker (SG4)2

<400>  131

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   10  


<210>  132
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker G4(SG4)2

<400>  132

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   10                  


<210>  133
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  133

Gly Ser Pro Gly Ser Ser Ser Ser Gly Ser 
1               5                   10  


<210>  134
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker (G4S)3

<400>  134

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  135
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker (G4S)4

<400>  135

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Gly Gly Gly Ser 
            20  


<210>  136
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  136

Gly Ser Gly Ser Gly Ser Gly Ser 
1               5               


<210>  137
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  137

Gly Ser Gly Ser Gly Asn Gly Ser 
1               5               


<210>  138
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  138

Gly Gly Ser Gly Ser Gly Ser Gly 
1               5               


<210>  139
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  139

Gly Gly Ser Gly Ser Gly 
1               5       


<210>  140
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  140

Gly Gly Ser Gly 
1               


<210>  141
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  141

Gly Gly Ser Gly Asn Gly Ser Gly 
1               5               


<210>  142
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  142

Gly Gly Asn Gly Ser Gly Ser Gly 
1               5               


<210>  143
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide linker

<400>  143

Gly Gly Asn Gly Ser Gly 
1               5       


<210>  144
<211>  461
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 1+1 PD1/LAG3 0725 (1+1 trans)

<400>  144

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


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


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


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile 
            100                 105                 110         


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


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


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


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


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


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


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


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln 
225                 230                 235                 240 


Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
                245                 250                 255     


Leu Ser Cys Ala Ala Ser Gly Phe Ile Phe Asp Asp Tyr Thr Met Asn 
            260                 265                 270         


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
        275                 280                 285             


Ser Trp Asp Gly Gly Gly Thr Tyr Tyr Thr Asp Ser Val Lys Gly Arg 
    290                 295                 300                 


Phe Thr Ile Ser Arg Asp Asp Phe Lys Asn Thr Leu Tyr Leu Gln Met 
305                 310                 315                 320 


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly 
                325                 330                 335     


Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly Gln Gly Thr 
            340                 345                 350         


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


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    370                 375                 380                 


Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
385                 390                 395                 400 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                405                 410                 415     


Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
            420                 425                 430         


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        435                 440                 445             


Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys 
    450                 455                 460     


<210>  145
<211>  685
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain 2 of 2+1 PD1/LAG3 0750 (2+1 trans)

<400>  145

Glu Val Gln Leu Leu 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 Ile Phe Asp Asp Tyr 
            20                  25                  30          


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


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


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


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


Ala Lys Gly Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln 
    450                 455                 460                 


Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
465                 470                 475                 480 


Leu Ser Cys Ala Ala Ser Gly Phe Ile Phe Asp Asp Tyr Thr Met Asn 
                485                 490                 495     


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val Ile 
            500                 505                 510         


Ser Trp Asp Gly Gly Gly Thr Tyr Tyr Thr Asp Ser Val Lys Gly Arg 
        515                 520                 525             


Phe Thr Ile Ser Arg Asp Asp Phe Lys Asn Thr Leu Tyr Leu Gln Met 
    530                 535                 540                 


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly 
545                 550                 555                 560 


Leu Thr Asp Thr Thr Leu Tyr Gly Ser Asp Tyr Trp Gly Gln Gly Thr 
                565                 570                 575     


Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
            580                 585                 590         


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
        595                 600                 605             


Cys Leu Val Glu Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
    610                 615                 620                 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
625                 630                 635                 640 


Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
                645                 650                 655     


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
            660                 665                 670         


Asn Thr Lys Val Asp Glu Lys Val Glu Pro Lys Ser Cys 
        675                 680                 685 


<210>  146
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CEA (CEA TCB)

<400>  146

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 Lys Ala Ser Ala Ala Val Gly Thr Tyr 
            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 Tyr Arg Lys Arg 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 His Gln Tyr Tyr Thr Tyr Pro Leu 
                85                  90                  95      


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


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


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


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


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


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


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


Ser Phe Asn Arg Gly Glu Cys 
    210                 215 


<210>  147
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CD3 (CEA TCB)

<400>  147

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


Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
            20                  25                  30          


Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Ala Phe Arg Gly 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Thr Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala 
65                  70                  75                  80  


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


Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Ser Ala 
            100                 105                 110         


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


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


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
145                 150                 155                 160 


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


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


Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys 
        195                 200                 205             


Val Glu Pro Lys Ser Cys 
    210                 


<210>  148
<211>  694
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA CD3 crossfab VHck fc knob P329GLALA (CEA TCB)

<400>  148

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 Thr Phe Thr Glu Phe 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Lys Thr Gly Glu Ala Thr Tyr Val Glu Glu Phe 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu 
225                 230                 235                 240 


Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
                245                 250                 255     


Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr Ala Met Asn Trp Val 
            260                 265                 270         


Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Arg Ile Arg Ser 
        275                 280                 285             


Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
    290                 295                 300                 


Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met 
305                 310                 315                 320 


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His 
                325                 330                 335     


Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln 
            340                 345                 350         


Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val 
        355                 360                 365             


Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 
    370                 375                 380                 


Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 
385                 390                 395                 400 


Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 
                405                 410                 415     


Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 
            420                 425                 430         


Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 
        435                 440                 445             


Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 
    450                 455                 460                 


Gly Glu Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
465                 470                 475                 480 


Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                485                 490                 495     


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            500                 505                 510         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        515                 520                 525             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    530                 535                 540                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
545                 550                 555                 560 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly 
                565                 570                 575     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            580                 585                 590         


Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn 
        595                 600                 605             


Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    610                 615                 620                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
625                 630                 635                 640 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                645                 650                 655     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            660                 665                 670         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        675                 680                 685             


Ser Leu Ser Pro Gly Lys 
    690                 


<210>  149
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA VHCH1 Fc hole P329GLALA (CEA TCB)

<400>  149

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 Thr Phe Thr Glu Phe 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Lys Thr Gly Glu Ala Thr Tyr Val Glu Glu Phe 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  150
<211>  232
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3 VH-CL (CEACAM5 TCB)

<400>  150

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


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


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


Ser Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
            100                 105                 110         


Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val 
        115                 120                 125             


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


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


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


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


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


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


Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230         


<210>  151
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEACAM5 VH-CH1(EE)-Fc (hole, P329G LALA)

<400>  151

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro 
    


<210>  152
<211>  674
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEACAM5 VH-CH1(EE)-CD3 VL-CH1-Fc (knob, P329G LALA)

<400>  152

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


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


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


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


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


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


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


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


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


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


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


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


Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ala Val Val Thr 
225                 230                 235                 240 


Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr 
                245                 250                 255     


Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp 
            260                 265                 270         


Val Gln Glu Lys Pro Gly Gln Ala Phe Arg Gly Leu Ile Gly Gly Thr 
        275                 280                 285             


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


Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Ala Gln Pro Glu Asp Glu 
305                 310                 315                 320 


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


Gly Gly Thr Lys Leu Thr Val Leu Ser Ser Ala Ser Thr Lys Gly Pro 
            340                 345                 350         


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


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


Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
385                 390                 395                 400 


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
                405                 410                 415     


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
            420                 425                 430         


His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 
        435                 440                 445             


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    450                 455                 460                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
465                 470                 475                 480 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                485                 490                 495     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            500                 505                 510         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        515                 520                 525             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    530                 535                 540                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro 
545                 550                 555                 560 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                565                 570                 575     


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
            580                 585                 590         


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        595                 600                 605             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    610                 615                 620                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
625                 630                 635                 640 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                645                 650                 655     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            660                 665                 670         


Ser Pro 
        


<210>  153
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEACAM5  VL-CL(RK)

<400>  153

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 Gly Glu Ser Val Asp Ile Phe 
            20                  25                  30          


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


Arg Leu Leu Ile Tyr Arg Ala Ser Asn Arg Ala Thr Gly Ile 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 Gln Thr Asn 
                85                  90                  95      


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


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Arg Lys 
        115                 120                 125             


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


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


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


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


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


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


<210>  154
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR1

<400>  154

Glu Phe Gly Met Asn 
1               5   


<210>  155
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR2

<400>  155

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


Gly 
    


<210>  156
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR3

<400>  156

Trp Asp Phe Ala Tyr Tyr Val Glu Ala Met Asp Tyr 
1               5                   10          


<210>  157
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR1

<400>  157

Lys Ala Ser Ala Ala Val Gly Thr Tyr Val Ala 
1               5                   10      


<210>  158
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR2

<400>  158

Ser Ala Ser Tyr Arg Lys Arg 
1               5           


<210>  159
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR3

<400>  159

His Gln Tyr Tyr Thr Tyr Pro Leu Phe Thr 
1               5                   10  


<210>  160
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA VH

<400>  160

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 Thr Phe Thr Glu Phe 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Lys Thr Gly Glu Ala Thr Tyr Val Glu Glu Phe 
    50                  55                  60                  


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


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


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


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  161
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA VL

<400>  161

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 Lys Ala Ser Ala Ala Val Gly Thr Tyr 
            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 Tyr Arg Lys Arg 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 His Gln Tyr Tyr Thr Tyr Pro Leu 
                85                  90                  95      


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


<210>  162
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR1 (CEACAM5)

<400>  162

Asp Thr Tyr Met His 
1               5   


<210>  163
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR2 (CEACAM5)

<400>  163

Arg Ile Asp Pro Ala Asn Gly Asn Ser Lys Tyr Val Pro Lys Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  164
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-HCDR3 (CEACAM5)

<400>  164

Phe Gly Tyr Tyr Val Ser Asp Tyr Ala Met Ala Tyr 
1               5                   10          


<210>  165
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR1 (CEACAM5)

<400>  165

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


<210>  166
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR2 (CEACAM5)

<400>  166

Arg Ala Ser Asn Arg Ala Thr 
1               5           


<210>  167
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA-LCDR3 (CEACAM5)

<400>  167

Gln Gln Thr Asn Glu Asp Pro Tyr Thr 
1               5                   


<210>  168
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA VH (CEACAM5)

<400>  168

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


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


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


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


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


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  169
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CEA VL (CEACAM5)

<400>  169

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 Gly Glu Ser Val Asp Ile Phe 
            20                  25                  30          


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


Arg Leu Leu Ile Tyr Arg Ala Ser Asn Arg Ala Thr Gly Ile 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 Gln Thr Asn 
                85                  90                  95      


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


