                         SEQUENCE LISTING

<110>  SYNTHORX, INC.
 
<120>  LUNG CANCER COMBINATION THERAPY WITH IL-2 CONJUGATES AND 
       PEMBROLIZUMAB

<130>  01183-0106-00PCT

<150>  US 63/149,078
<151>  2021-02-12

<150>  US 63/253,903
<151>  2021-10-08

<150>  US 63/276,954
<151>  2021-11-08

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  132
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL-2 conjugate

<400>  1

Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu 
1               5                   10                  15      


Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn 
            20                  25                  30          


Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys 
        35                  40                  45              


Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro 
    50                  55                  60                  


Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg 
65                  70                  75                  80  


Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys 
                85                  90                  95      


Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr 
            100                 105                 110         


Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile Ile 
        115                 120                 125             


Ser Thr Leu Thr 
    130         


<210>  2
<211>  132
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL-2 conjugate


<220>
<221>  misc_feature
<222>  (64)..(64)
<223>  N6-((2-azidoethoxy)-carbonyl)-L-lysine stably-conjugated to PEG 
       via DBCO-mediated click chemistry

<400>  2

Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu 
1               5                   10                  15      


Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn 
            20                  25                  30          


Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys 
        35                  40                  45              


Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Xaa 
    50                  55                  60                  


Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg 
65                  70                  75                  80  


Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys 
                85                  90                  95      


Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr 
            100                 105                 110         


Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile Ile 
        115                 120                 125             


Ser Thr Leu Thr 
    130         


<210>  3
<211>  133
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL-2 conjugate


<220>
<221>  misc_feature
<222>  (65)..(65)
<223>  N6-((2-azidoethoxy)-carbonyl)-L-lysine stably-conjugated to PEG 
       via DBCO-mediated click chemistry

<400>  3

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


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Xaa Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr 
    130             


<210>  4
<211>  133
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL-2 conjugate

<400>  4

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


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr 
    130             


<210>  5

<400>  5
000

<210>  6

<400>  6
000

<210>  7

<400>  7
000

<210>  8

<400>  8
000

<210>  9

<400>  9
000

<210>  10

<400>  10
000

<210>  11
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hPD-1.09A light chain CDR1

<400>  11

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


<210>  12
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hPD-1.09A light chain CDR2

<400>  12

Leu Ala Ser Tyr Leu Glu Ser 
1               5           


<210>  13
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hPD-1.09A light chain CDR3

<400>  13

Gln His Ser Arg Asp Leu Pro Leu Thr 
1               5                   


<210>  14
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL of pembrolizumab

<400>  14

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


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


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


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


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


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


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


<210>  15
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain of pembrolizumab

<400>  15

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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  16
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hPD-1.09A heavy chain CDR1

<400>  16

Asn Tyr Tyr Met Tyr 
1               5   


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

<220>
<223>  hPD-1.09A heavy chain CDR2

<400>  17

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


Asn 
    


<210>  18
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hPD-1.09A heavy chain CDR3

<400>  18

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


<210>  19
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of pembrolizumab

<400>  19

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


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


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


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


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


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


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


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  20
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain of pembrolizumab

<400>  20

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


