                         SEQUENCE LISTING

<110>  SynAffix B.V.
 
<120>  Novel antibody-conjugates with improved therapeutic index for 
       targeting CD30 tumours and method for improving therapeutic index
        of antibody-conjugates

<130>  P6061998PCT

<150>  EP16173599.8
<151>  2016-06-08

<150>  JP2016-155927
<151>  2016-08-08

<150>  EP16154739.3
<151>  2016-02-08

<150>  EP16154712.0
<151>  2016-02-08

<160>  2     

<170>  PatentIn version 3.5

<210>  1
<211>  1258
<212>  PRT
<213>  Artificial sequence

<220>
<223>  fusion protein EndoSH

<400>  1

Met Pro Ser Ile Asp Ser Leu His Tyr Leu Ser Glu Asn Ser Lys Lys 
1               5                   10                  15      


Glu Phe Lys Glu Glu Leu Ser Lys Ala Gly Gln Glu Ser Gln Lys Val 
            20                  25                  30          


Lys Glu Ile Leu Ala Lys Ala Gln Gln Ala Asp Lys Gln Ala Gln Glu 
        35                  40                  45              


Leu Ala Lys Met Lys Ile Pro Glu Lys Ile Pro Met Lys Pro Leu His 
    50                  55                  60                  


Gly Pro Leu Tyr Gly Gly Tyr Phe Arg Thr Trp His Asp Lys Thr Ser 
65                  70                  75                  80  


Asp Pro Thr Glu Lys Asp Lys Val Asn Ser Met Gly Glu Leu Pro Lys 
                85                  90                  95      


Glu Val Asp Leu Ala Phe Ile Phe His Asp Trp Thr Lys Asp Tyr Ser 
            100                 105                 110         


Leu Phe Trp Lys Glu Leu Ala Thr Lys His Val Pro Lys Leu Asn Lys 
        115                 120                 125             


Gln Gly Thr Arg Val Ile Arg Thr Ile Pro Trp Arg Phe Leu Ala Gly 
    130                 135                 140                 


Gly Asp Asn Ser Gly Ile Ala Glu Asp Thr Ser Lys Tyr Pro Asn Thr 
145                 150                 155                 160 


Pro Glu Gly Asn Lys Ala Leu Ala Lys Ala Ile Val Asp Glu Tyr Val 
                165                 170                 175     


Tyr Lys Tyr Asn Leu Asp Gly Leu Asp Val Asp Val Glu His Asp Ser 
            180                 185                 190         


Ile Pro Lys Val Asp Lys Lys Glu Asp Thr Ala Gly Val Glu Arg Ser 
        195                 200                 205             


Ile Gln Val Phe Glu Glu Ile Gly Lys Leu Ile Gly Pro Lys Gly Val 
    210                 215                 220                 


Asp Lys Ser Arg Leu Phe Ile Met Asp Ser Thr Tyr Met Ala Asp Lys 
225                 230                 235                 240 


Asn Pro Leu Ile Glu Arg Gly Ala Pro Tyr Ile Asn Leu Leu Leu Val 
                245                 250                 255     


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


Asn Arg Pro Glu Lys Thr Met Glu Glu Arg Trp Gln Gly Tyr Ser Lys 
        275                 280                 285             


Tyr Ile Arg Pro Glu Gln Tyr Met Ile Gly Phe Ser Phe Tyr Glu Glu 
    290                 295                 300                 


Asn Ala Gln Glu Gly Asn Leu Trp Tyr Asp Ile Asn Ser Arg Lys Asp 
305                 310                 315                 320 


Glu Asp Lys Ala Asn Gly Ile Asn Thr Asp Ile Thr Gly Thr Arg Ala 
                325                 330                 335     


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


Ile Phe Ser Tyr Ala Ile Asp Arg Asp Gly Val Ala His Gln Pro Lys 
        355                 360                 365             


Lys Tyr Ala Lys Gln Lys Glu Phe Lys Asp Ala Thr Asp Asn Ile Phe 
    370                 375                 380                 


His Ser Asp Tyr Ser Val Ser Lys Ala Leu Lys Thr Val Met Leu Lys 
385                 390                 395                 400 


Asp Lys Ser Tyr Asp Leu Ile Asp Glu Lys Asp Phe Pro Asp Lys Ala 
                405                 410                 415     


Leu Arg Glu Ala Val Met Ala Gln Val Gly Thr Arg Lys Gly Asp Leu 
            420                 425                 430         


Glu Arg Phe Asn Gly Thr Leu Arg Leu Asp Asn Pro Ala Ile Gln Ser 
        435                 440                 445             


Leu Glu Gly Leu Asn Lys Phe Lys Lys Leu Ala Gln Leu Asp Leu Ile 
    450                 455                 460                 


Gly Leu Ser Arg Ile Thr Lys Leu Asp Arg Ser Val Leu Pro Ala Asn 
465                 470                 475                 480 


Met Lys Pro Gly Lys Asp Thr Leu Glu Thr Val Leu Glu Thr Tyr Lys 
                485                 490                 495     


Lys Asp Asn Lys Glu Glu Pro Ala Thr Ile Pro Pro Val Ser Leu Lys 
            500                 505                 510         


Val Ser Gly Leu Thr Gly Leu Lys Glu Leu Asp Leu Ser Gly Phe Asp 
        515                 520                 525             


Arg Glu Thr Leu Ala Gly Leu Asp Ala Ala Thr Leu Thr Ser Leu Glu 
    530                 535                 540                 


Lys Val Asp Ile Ser Gly Asn Lys Leu Asp Leu Ala Pro Gly Thr Glu 
545                 550                 555                 560 


Asn Arg Gln Ile Phe Asp Thr Met Leu Ser Thr Ile Ser Asn His Val 
                565                 570                 575     


Gly Ser Asn Glu Gln Thr Val Lys Phe Asp Lys Gln Lys Pro Thr Gly 
            580                 585                 590         


His Tyr Pro Asp Thr Tyr Gly Lys Thr Ser Leu Arg Leu Pro Val Ala 
        595                 600                 605             


Asn Glu Lys Val Asp Leu Gln Ser Gln Leu Leu Phe Gly Thr Val Thr 
    610                 615                 620                 


Asn Gln Gly Thr Leu Ile Asn Ser Glu Ala Asp Tyr Lys Ala Tyr Gln 
625                 630                 635                 640 


Asn His Lys Ile Ala Gly Arg Ser Phe Val Asp Ser Asn Tyr His Tyr 
                645                 650                 655     


Asn Asn Phe Lys Val Ser Tyr Glu Asn Tyr Thr Val Lys Val Thr Asp 
            660                 665                 670         


Ser Thr Leu Gly Thr Thr Thr Asp Lys Thr Leu Ala Thr Asp Lys Glu 
        675                 680                 685             


Glu Thr Tyr Lys Val Asp Phe Phe Ser Pro Ala Asp Lys Thr Lys Ala 
    690                 695                 700                 


Val His Thr Ala Lys Val Ile Val Gly Asp Glu Lys Thr Met Met Val 
705                 710                 715                 720 


Asn Leu Ala Glu Gly Ala Thr Val Ile Gly Gly Ser Ala Asp Pro Val 
                725                 730                 735     


Asn Ala Arg Lys Val Phe Asp Gly Gln Leu Gly Ser Glu Thr Asp Asn 
            740                 745                 750         


Ile Ser Leu Gly Trp Asp Ser Lys Gln Ser Ile Ile Phe Lys Leu Lys 
        755                 760                 765             


Glu Asp Gly Leu Ile Lys His Trp Arg Phe Phe Asn Asp Ser Ala Arg 
    770                 775                 780                 


Asn Pro Glu Thr Thr Asn Lys Pro Ile Gln Glu Ala Ser Leu Gln Ile 
785                 790                 795                 800 


Phe Asn Ile Lys Asp Tyr Asn Leu Asp Asn Leu Leu Glu Asn Pro Asn 
                805                 810                 815     


Lys Phe Asp Asp Glu Lys Tyr Trp Ile Thr Val Asp Thr Tyr Ser Ala 
            820                 825                 830         


Gln Gly Glu Arg Ala Thr Ala Phe Ser Asn Thr Leu Asn Asn Ile Thr 
        835                 840                 845             


Ser Lys Tyr Trp Arg Val Val Phe Asp Thr Lys Gly Asp Arg Tyr Ser 
    850                 855                 860                 


Ser Pro Val Val Pro Glu Leu Gln Ile Leu Gly Tyr Pro Leu Pro Asn 
865                 870                 875                 880 


Ala Asp Thr Ile Met Lys Thr Val Thr Thr Ala Lys Glu Leu Ser Gln 
                885                 890                 895     


Gln Lys Asp Lys Phe Ser Gln Lys Met Leu Asp Glu Leu Lys Ile Lys 
            900                 905                 910         


Glu Met Ala Leu Glu Thr Ser Leu Asn Ser Lys Ile Phe Asp Val Thr 
        915                 920                 925             


Ala Ile Asn Ala Asn Ala Gly Val Leu Lys Asp Cys Ile Glu Lys Arg 
    930                 935                 940                 


Gln Leu Leu Lys Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
945                 950                 955                 960 


Gly Gly Gly Ser His His His His His His Glu Phe Gly Gly Gly Gly 
                965                 970                 975     


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Pro Ala Pro Val 
            980                 985                 990         


Lys Gln Gly Pro Thr Ser Val Ala  Tyr Val Glu Val Asn  Asn Asn Ser 
        995                 1000                 1005             


Met Leu  Asn Val Gly Lys Tyr  Thr Leu Ala Asp Gly  Gly Gly Asn 
    1010                 1015                 1020             


Ala Phe  Asp Val Ala Val Ile  Phe Ala Ala Asn Ile  Asn Tyr Asp 
    1025                 1030                 1035             


Thr Gly  Thr Lys Thr Ala Tyr  Leu His Phe Asn Glu  Asn Val Gln 
    1040                 1045                 1050             


Arg Val  Leu Asp Asn Ala Val  Thr Gln Ile Arg Pro  Leu Gln Gln 
    1055                 1060                 1065             


Gln Gly  Ile Lys Val Leu Leu  Ser Val Leu Gly Asn  His Gln Gly 
    1070                 1075                 1080             


Ala Gly  Phe Ala Asn Phe Pro  Ser Gln Gln Ala Ala  Ser Ala Phe 
    1085                 1090                 1095             


Ala Lys  Gln Leu Ser Asp Ala  Val Ala Lys Tyr Gly  Leu Asp Gly 
    1100                 1105                 1110             


Val Asp  Phe Asp Asp Glu Tyr  Ala Glu Tyr Gly Asn  Asn Gly Thr 
    1115                 1120                 1125             


Ala Gln  Pro Asn Asp Ser Ser  Phe Val His Leu Val  Thr Ala Leu 
    1130                 1135                 1140             


Arg Ala  Asn Met Pro Asp Lys  Ile Ile Ser Leu Tyr  Asn Ile Gly 
    1145                 1150                 1155             


Pro Ala  Ala Ser Arg Leu Ser  Tyr Gly Gly Val Asp  Val Ser Asp 
    1160                 1165                 1170             


Lys Phe  Asp Tyr Ala Trp Asn  Pro Tyr Tyr Gly Thr  Trp Gln Val 
    1175                 1180                 1185             


Pro Gly  Ile Ala Leu Pro Lys  Ala Gln Leu Ser Pro  Ala Ala Val 
    1190                 1195                 1200             


Glu Ile  Gly Arg Thr Ser Arg  Ser Thr Val Ala Asp  Leu Ala Arg 
    1205                 1210                 1215             


Arg Thr  Val Asp Glu Gly Tyr  Gly Val Tyr Leu Thr  Tyr Asn Leu 
    1220                 1225                 1230             


Asp Gly  Gly Asp Arg Thr Ala  Asp Val Ser Ala Phe  Thr Arg Glu 
    1235                 1240                 1245             


Leu Tyr  Gly Ser Glu Ala Val  Arg Thr Pro 
    1250                 1255             


<210>  2
<211>  410
<212>  PRT
<213>  Artificial sequence

<220>
<223>  His-TnGalNAcT(33-421)

<400>  2

Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro 
1               5                   10                  15      


Arg Gly Ser His Met Ser Pro Leu Arg Thr Tyr Leu Tyr Thr Pro Leu 
            20                  25                  30          


Tyr Asn Ala Thr Gln Pro Thr Leu Arg Asn Val Glu Arg Leu Ala Ala 
        35                  40                  45              


Asn Trp Pro Lys Lys Ile Pro Ser Asn Tyr Ile Glu Asp Ser Glu Glu 
    50                  55                  60                  


Tyr Ser Ile Lys Asn Ile Ser Leu Ser Asn His Thr Thr Arg Ala Ser 
65                  70                  75                  80  


Val Val His Pro Pro Ser Ser Ile Thr Glu Thr Ala Ser Lys Leu Asp 
                85                  90                  95      


Lys Asn Met Thr Ile Gln Asp Gly Ala Phe Ala Met Ile Ser Pro Thr 
            100                 105                 110         


Pro Leu Leu Ile Thr Lys Leu Met Asp Ser Ile Lys Ser Tyr Val Thr 
        115                 120                 125             


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


Cys Asp Ser Met Pro Pro Asp Leu Gly Pro Ile Thr Leu Asn Lys Thr 
145                 150                 155                 160 


Glu Leu Glu Leu Glu Trp Val Glu Lys Lys Phe Pro Glu Val Glu Trp 
                165                 170                 175     


Gly Gly Arg Tyr Ser Pro Pro Asn Cys Thr Ala Arg His Arg Val Ala 
            180                 185                 190         


Ile Ile Val Pro Tyr Arg Asp Arg Gln Gln His Leu Ala Ile Phe Leu 
        195                 200                 205             


Asn His Met His Pro Phe Leu Met Lys Gln Gln Ile Glu Tyr Gly Ile 
    210                 215                 220                 


Phe Ile Val Glu Gln Glu Gly Asn Lys Asp Phe Asn Arg Ala Lys Leu 
225                 230                 235                 240 


Met Asn Val Gly Phe Val Glu Ser Gln Lys Leu Val Ala Glu Gly Trp 
                245                 250                 255     


Gln Cys Phe Val Phe His Asp Ile Asp Leu Leu Pro Leu Asp Thr Arg 
            260                 265                 270         


Asn Leu Tyr Ser Cys Pro Arg Gln Pro Arg His Met Ser Ala Ser Ile 
        275                 280                 285             


Asp Lys Leu His Phe Lys Leu Pro Tyr Glu Asp Ile Phe Gly Gly Val 
    290                 295                 300                 


Ser Ala Met Thr Leu Glu Gln Phe Thr Arg Val Asn Gly Phe Ser Asn 
305                 310                 315                 320 


Lys Tyr Trp Gly Trp Gly Gly Glu Asp Asp Asp Met Ser Tyr Arg Leu 
                325                 330                 335     


Lys Lys Ile Asn Tyr His Ile Ala Arg Tyr Lys Met Ser Ile Ala Arg 
            340                 345                 350         


Tyr Ala Met Leu Asp His Lys Lys Ser Thr Pro Asn Pro Lys Arg Tyr 
        355                 360                 365             


Gln Leu Leu Ser Gln Thr Ser Lys Thr Phe Gln Lys Asp Gly Leu Ser 
    370                 375                 380                 


Thr Leu Glu Tyr Glu Leu Val Gln Val Val Gln Tyr His Leu Tyr Thr 
385                 390                 395                 400 


His Ile Leu Val Asn Ile Asp Glu Arg Ser 
                405                 410 


