               SEQUENCE LISTING

<110> GAMAMABS PHARMA

<120> AMHRII-binding antibody drug conjugates and their use thereof in the treatment of cancers

<130> PR88008

<150> EP19306066.2
<151> 2019-09-03

<160> 12

<170> BiSSAP 1.3.6

<210> 1
<211> 13
<212> PRT
<213> Artificial Sequence


<220> 
<223> H-CDR1

<400> 1
Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr His Ile His 
1               5                   10              

<210> 2
<211> 17
<212> PRT
<213> Artificial Sequence


<220> 
<223> H-CDR2

<400> 2
Trp Ile Tyr Pro Gly Asp Asp Ser Thr Lys Tyr Ser Gln Lys Phe Gln 
1               5                   10                  15      
Gly 
    

<210> 3
<211> 6
<212> PRT
<213> Artificial Sequence


<220> 
<223> H-CDR3

<400> 3
Gly Asp Arg Phe Ala Tyr 
1               5       

<210> 4
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> L-CDR1

<400> 4
Arg Ala Ser Ser Ser Val Arg Tyr Ile Ala 
1               5                   10  

<210> 5
<211> 7
<212> PRT
<213> Artificial Sequence


<220> 
<223> L-CDR2

<400> 5
Pro Thr Ser Ser Leu Glu Ser 
1               5           

<210> 6
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> L-CDR3

<400> 6
Leu Gln Trp Ser Ser Tyr Pro Trp Thr Phe 
1               5                   10  

<210> 7
<211> 115
<212> PRT
<213> Artificial Sequence


<220> 
<223> heavy chain variable region

<400> 7
Gln Val Arg 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 Ser Tyr 
            20                  25                  30          
His Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Trp Ile Tyr Pro Gly Asp Asp Ser Thr Lys Tyr Ser Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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      
Thr Arg Gly Asp Arg Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr 
            100                 105                 110         
Val Ser Ser 
        115 

<210> 8
<211> 106
<212> PRT
<213> Artificial Sequence


<220> 
<223> light chain variable region

<400> 8
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Arg Tyr Ile 
            20                  25                  30          
Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Thr Tyr 
        35                  40                  45              
Pro Thr Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
    50                  55                  60                  
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp 
65                  70                  75                  80  
Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Trp Ser Ser Tyr Pro Trp Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105     

<210> 9
<211> 446
<212> PRT
<213> Artificial Sequence


<220> 
<223> heavy chain

<400> 9
Gln Val Arg 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 Ser Tyr 
            20                  25                  30          
His Ile His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Trp Ile Tyr Pro Gly Asp Asp Ser Thr Lys Tyr Ser Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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      
Thr Arg Gly Asp Arg Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr 
            100                 105                 110         
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
        115                 120                 125             
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 
                165                 170                 175     
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 
            180                 185                 190         
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 
        195                 200                 205             
Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 
    210                 215                 220                 
Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Cys Val Phe 
225                 230                 235                 240 
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                245                 250                 255     
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
            260                 265                 270         
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
        275                 280                 285             
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
    290                 295                 300                 
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                325                 330                 335     
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
    370                 375                 380                 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
385                 390                 395                 400 
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445     

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


<220> 
<223> light chain

<400> 10
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Arg Tyr Ile 
            20                  25                  30          
Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Thr Tyr 
        35                  40                  45              
Pro Thr Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
    50                  55                  60                  
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp 
65                  70                  75                  80  
Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Trp Ser Ser Tyr Pro Trp Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 
            100                 105                 110         
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
        115                 120                 125             
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
    130                 135                 140                 
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
145                 150                 155                 160 
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                165                 170                 175     
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
            180                 185                 190         
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
        195                 200                 205             
Asn Arg Gly Glu Cys 
    210             

<210> 11
<211> 556
<212> PRT
<213> Artificial Sequence


<220> 
<223> human AMHRII sequence lacking its signal peptide

<400> 11
Pro Pro Asn Arg Arg Thr Cys Val Phe Phe Glu Ala Pro Gly Val Arg 
1               5                   10                  15      
Gly Ser Thr Lys Thr Leu Gly Glu Leu Leu Asp Thr Gly Thr Glu Leu 
            20                  25                  30          
Pro Arg Ala Ile Arg Cys Leu Tyr Ser Arg Cys Cys Phe Gly Ile Trp 
        35                  40                  45              
Asn Leu Thr Gln Asp Arg Ala Gln Val Glu Met Gln Gly Cys Arg Asp 
    50                  55                  60                  
Ser Asp Glu Pro Gly Cys Glu Ser Leu His Cys Asp Pro Ser Pro Arg 
65                  70                  75                  80  
Ala His Pro Ser Pro Gly Ser Thr Leu Phe Thr Cys Ser Cys Gly Thr 
                85                  90                  95      
Asp Phe Cys Asn Ala Asn Tyr Ser His Leu Pro Pro Pro Gly Ser Pro 
            100                 105                 110         
Gly Thr Pro Gly Ser Gln Gly Pro Gln Ala Ala Pro Gly Glu Ser Ile 
        115                 120                 125             
Trp Met Ala Leu Val Leu Leu Gly Leu Phe Leu Leu Leu Leu Leu Leu 
    130                 135                 140                 
Leu Gly Ser Ile Ile Leu Ala Leu Leu Gln Arg Lys Asn Tyr Arg Val 
145                 150                 155                 160 
Arg Gly Glu Pro Val Pro Glu Pro Arg Pro Asp Ser Gly Arg Asp Trp 
                165                 170                 175     
Ser Val Glu Leu Gln Glu Leu Pro Glu Leu Cys Phe Ser Gln Val Ile 
            180                 185                 190         
Arg Glu Gly Gly His Ala Val Val Trp Ala Gly Gln Leu Gln Gly Lys 
        195                 200                 205             
Leu Val Ala Ile Lys Ala Phe Pro Pro Arg Ser Val Ala Gln Phe Gln 
    210                 215                 220                 
Ala Glu Arg Ala Leu Tyr Glu Leu Pro Gly Leu Gln His Asp His Ile 
225                 230                 235                 240 
Val Arg Phe Ile Thr Ala Ser Arg Gly Gly Pro Gly Arg Leu Leu Ser 
                245                 250                 255     
Gly Pro Leu Leu Val Leu Glu Leu His Pro Lys Gly Ser Leu Cys His 
            260                 265                 270         
Tyr Leu Thr Gln Tyr Thr Ser Asp Trp Gly Ser Ser Leu Arg Met Ala 
        275                 280                 285             
Leu Ser Leu Ala Gln Gly Leu Ala Phe Leu His Glu Glu Arg Trp Gln 
    290                 295                 300                 
Asn Gly Gln Tyr Lys Pro Gly Ile Ala His Arg Asp Leu Ser Ser Gln 
305                 310                 315                 320 
Asn Val Leu Ile Arg Glu Asp Gly Ser Cys Ala Ile Gly Asp Leu Gly 
                325                 330                 335     
Leu Ala Leu Val Leu Pro Gly Leu Thr Gln Pro Pro Ala Trp Thr Pro 
            340                 345                 350         
Thr Gln Pro Gln Gly Pro Ala Ala Ile Met Glu Ala Gly Thr Gln Arg 
        355                 360                 365             
Tyr Met Ala Pro Glu Leu Leu Asp Lys Thr Leu Asp Leu Gln Asp Trp 
    370                 375                 380                 
Gly Met Ala Leu Arg Arg Ala Asp Ile Tyr Ser Leu Ala Leu Leu Leu 
385                 390                 395                 400 
Trp Glu Ile Leu Ser Arg Cys Pro Asp Leu Arg Pro Asp Ser Ser Pro 
                405                 410                 415     
Pro Pro Phe Gln Leu Ala Tyr Glu Ala Glu Leu Gly Asn Thr Pro Thr 
            420                 425                 430         
Ser Asp Glu Leu Trp Ala Leu Ala Val Gln Glu Arg Arg Arg Pro Tyr 
        435                 440                 445             
Ile Pro Ser Thr Trp Arg Cys Phe Ala Thr Asp Pro Asp Gly Leu Arg 
    450                 455                 460                 
Glu Leu Leu Glu Asp Cys Trp Asp Ala Asp Pro Glu Ala Arg Leu Thr 
465                 470                 475                 480 
Ala Glu Cys Val Gln Gln Arg Leu Ala Ala Leu Ala His Pro Gln Glu 
                485                 490                 495     
Ser His Pro Phe Pro Glu Ser Cys Pro Arg Gly Cys Pro Pro Leu Cys 
            500                 505                 510         
Pro Glu Asp Cys Thr Ser Ile Pro Ala Pro Thr Ile Leu Pro Cys Arg 
        515                 520                 525             
Pro Gln Arg Ser Ala Cys His Phe Ser Val Gln Gln Gly Pro Cys Ser 
    530                 535                 540                 
Arg Asn Pro Gln Pro Ala Cys Thr Leu Ser Pro Val 
545                 550                 555     

<210> 12
<211> 17
<212> PRT
<213> Artificial Sequence


<220> 
<223> signal peptide of human AMHRII

<400> 12
Met Leu Gly Ser Leu Gly Leu Trp Ala Leu Leu Pro Thr Ala Val Glu 
1               5                   10                  15      
Ala 
    

