                         SEQUENCE LISTING

<110>  Merck Sharp & Dohme Corp.
       Abraham , Anson  K.
       Altura, Rachel, A.
       Wilson, Douglas, C.  
 
<120>  DOSING REGIMENS OF ANTI-ILT4 ANTIBODY OR ITS COMBINATION WITH 
       ANTI-PD-1 ANTIBODY FOR TREATING CANCER

<130>  25104-WO-PCT

<150>  63/079,976
<151>  2020-09-17 

<160>  22    

<170>  PatentIn version 3.5

<210>  1
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, VL-CDR1

<400>  1

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


<210>  2
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, VL-CDR2

<400>  2

Leu Ala Ser Tyr Leu Glu Ser 
1               5           


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

<220>
<223>  Pembrolizumab, VL-CDR3

<400>  3

Gln His Ser Arg Asp Leu Pro Leu Thr 
1               5                   


<210>  4
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, VL

<400>  4

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>  5
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, light chain

<400>  5

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


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


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


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


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


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


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 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>  6
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, VH-CDR1

<400>  6

Asn Tyr Tyr Met Tyr 
1               5   


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PEMBROLIZUMAB, VH-CDR2

<400>  7

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


Asn 
    


<210>  8
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, VH-CDR3

<400>  8

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


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

<220>
<223>  Pembrolizumab, VH

<400>  9

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>  10
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab, heavy chain

<400>  10

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         


<210>  11
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VL-CDR1

<400>  11

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


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

<220>
<223>  Anti-ILT4, VL-CDR2

<400>  12

Gly Asp Ser Asn Arg Pro Ser 
1               5           


<210>  13
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VL-CDR3

<400>  13

Gln Ser Phe Asp Asn Ser Leu Ser Ala Tyr Val 
1               5                   10      


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

<220>
<223>  Anti-ILT4, VL

<400>  14

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


Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ala Gly 
            20                  25                  30          


Tyr Asp Val His Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu 
        35                  40                  45              


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


Ser Val Ser Lys Ser Gly Ala Ser Ala Ser Leu Ala Ile Thr Gly Leu 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Phe Asp Asn Ser 
                85                  90                  95      


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


<210>  15
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, light chain

<400>  15

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


Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ala Gly 
            20                  25                  30          


Tyr Asp Val His Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu 
        35                  40                  45              


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


Ser Val Ser Lys Ser Gly Ala Ser Ala Ser Leu Ala Ile Thr Gly Leu 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Phe Asp Asn Ser 
                85                  90                  95      


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


Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu 
        115                 120                 125             


Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe 
    130                 135                 140                 


Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val 
145                 150                 155                 160 


Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys 
                165                 170                 175     


Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser 
            180                 185                 190         


His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu 
        195                 200                 205             


Lys Thr Val Ala Pro Thr Glu Cys Ser 
    210                 215         


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

<220>
<223>  Anti-ILT4, VH-CDR1

<400>  16

Gly Tyr Tyr Trp Ser 
1               5   


<210>  17
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VH-CDR2

<400>  17

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


<210>  18
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VH-CDR3

<400>  18

Leu Pro Thr Arg Trp Val Thr Thr Arg Tyr Phe Asp Leu 
1               5                   10              


<210>  19
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VH

<400>  19

Glu 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 Gly Tyr 
            20                  25                  30          


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


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


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


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


Arg Leu Pro Thr Arg Trp Val Thr Thr Arg Tyr Phe Asp Leu Trp Gly 
            100                 105                 110         


Arg Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  20
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, heavy chain

<400>  20

Glu 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 Gly Tyr 
            20                  25                  30          


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


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


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


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


Arg Leu Pro Thr Arg Trp Val Thr Thr Arg Tyr Phe Asp Leu Trp Gly 
            100                 105                 110         


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


Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 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 Lys Thr Tyr Thr Cys Asn Val Asp His 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  21
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4, VL-CDR2 consensus sequence


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X1 is N, Q, E or D

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X2 is S or A

<400>  21

Gly Xaa Xaa Asn Arg Pro Ser 
1               5           


<210>  22
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-ILT4 antibody, VH-CDR2 consensus sequence


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X is S or A

<400>  22

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


