                         SEQUENCE LISTING

<110>  TSENG, KUO-FU
 
<120>  PRO-ANTIBODY THAT REDUCES OFF-TARGET TOXICITY

<130>  AEBI:2000WO

<140>  PCT/US2021/013688
<141>  2021-01-15

<150>  62/962,555
<151>  2020-01-17

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  475
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide

<400>  1

Met Ile Asn Glu Phe Ser Ser Leu Ala Gly Ala Gln Arg Gln Arg Leu 
1               5                   10                  15      


Leu Gly Val Val Val Val Gln Ser Leu Val His His Gly Ala Ala Lys 
            20                  25                  30          


His Val Ala Leu Leu Pro Ser Ala Leu Val His Cys Gln Ile Ala Ser 
        35                  40                  45              


Glu Ser Lys Ala Ala Val Gly Ile Gln His Gly His Gly Gly Leu Val 
    50                  55                  60                  


Val Val Leu Gly Leu Ala Val Ala Phe Pro Phe His Gly Asp Ile Ala 
65                  70                  75                  80  


Arg Val Glu Ala Leu His Gln Thr Ala Gln Arg His Leu Ile Leu Gly 
                85                  90                  95      


Gln Leu Val Ser Ala Gly Arg Leu Gly Val His Leu Arg Leu Pro Arg 
            100                 105                 110         


Leu Ala Phe Gly Leu Ala Asp Gly Leu Leu Asn Gly Gly Gly Gln Ser 
        115                 120                 125             


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


Val Gln His Gly Gln His Gly His His Ser Ile Cys Gly Val Val Leu 
145                 150                 155                 160 


Leu Leu Ser Gly Leu Gly Phe Gly Val Val His Phe Asp Ala Val His 
                165                 170                 175     


Val Pro Val Lys Leu His Leu Gly Val Leu Met Ala Asp Val His His 
            180                 185                 190         


His Ala Cys His Leu Gly Cys Ser Arg Asp His Gln Cys Ile Leu Gly 
        195                 200                 205             


Phe Gly Arg Glu Gln Lys His Gly Arg Ser Ala Gln Gln Phe Gly Ser 
    210                 215                 220                 


Arg Thr Ala Arg Asn Arg Tyr His Arg Ala Leu Thr Pro Ile Val Glu 
225                 230                 235                 240 


Val Ala Gly Leu Thr Arg Thr Val Ile Ser Arg Gly Val Leu Gly Gly 
                245                 250                 255     


Tyr Arg Val Asn Leu Gln Lys Glu Leu Val Phe Arg Gly Val Thr Gly 
            260                 265                 270         


Asp Arg Asp Thr Arg Phe Asp Arg Arg Val Val Ile Gly Arg Thr Phe 
        275                 280                 285             


Ile Ile Asp Glu Thr His Pro Phe Asn Phe Leu Thr Trp Glu Leu Thr 
    290                 295                 300                 


Asp Pro Ile Pro Thr Ile Thr Gly Gly Asp Gly Gly Ala Gly Asn Arg 
305                 310                 315                 320 


Ala Arg Gln Ala Glu Arg Thr Gly Arg Ile Asn Gln Thr Arg Thr Arg 
                325                 330                 335     


Phe Phe Gln Phe Tyr Leu Ser Ala Tyr Val Leu Thr Pro Pro Phe Asp 
            340                 345                 350         


Phe Gln Leu Gly Ala Arg Thr Glu Arg Val Arg Ile Val Val Pro Leu 
        355                 360                 365             


Leu Ala Val Val Lys Arg Leu Val Phe Val Leu Asn Arg Arg Asn Gly 
    370                 375                 380                 


Gln Arg Glu Val Gly Thr Arg Ala Arg Thr Thr Glu Thr Val Arg Asn 
385                 390                 395                 400 


Ala Gly Val Thr Gly Arg Arg Val Val Asp Gln Gln Phe Arg Arg Leu 
                405                 410                 415     


Thr Arg Leu Leu His Val Pro Ile Gln Ile Val Gly Phe Arg Val Arg 
            420                 425                 430         


Val Glu Gln Ala Leu Arg Ala Phe Ala Arg Asp Gly Arg Phe Phe Thr 
        435                 440                 445             


Arg Arg His Ala Gln Arg Arg Trp Arg Leu Gly His His Asn Val Ser 
    450                 455                 460                 


Gly Gly Thr Trp Asn Pro Glu Gln Gln Tyr Pro 
465                 470                 475 


<210>  2
<211>  703
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide

<400>  2

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Val Ser Leu Gly Glu Arg Ala Thr Ile Ser Cys Lys Ser Ser Gln Ser 
        35                  40                  45              


Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln 
    50                  55                  60                  


Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg 
65                  70                  75                  80  


Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr 
            100                 105                 110         


Tyr Cys Gln Asn Asp Tyr Phe Tyr Pro Phe Thr Phe Gly Gln Gly Thr 
        115                 120                 125             


Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 
    130                 135                 140                 


Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 
145                 150                 155                 160 


Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 
                165                 170                 175     


Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 
            180                 185                 190         


Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 
        195                 200                 205             


Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 
    210                 215                 220                 


Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235                 240 


Gly Ser Ser Gly Arg Ser Glu Asn Ile Arg Thr Ala Gly Gly Ser Gln 
                245                 250                 255     


Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser 
            260                 265                 270         


Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Asn Tyr Leu 
        275                 280                 285             


Ile Glu Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly 
    290                 295                 300                 


Leu Ile Asn Pro Gly Ser Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys 
305                 310                 315                 320 


Gly Lys Ala Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met 
                325                 330                 335     


Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
            340                 345                 350         


Arg Val Tyr Tyr Gly Asn Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu 
        355                 360                 365             


Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
    370                 375                 380                 


Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
385                 390                 395                 400 


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


Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
            420                 425                 430         


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
        435                 440                 445             


Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
    450                 455                 460                 


Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
465                 470                 475                 480 


Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
                485                 490                 495     


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
            500                 505                 510         


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
        515                 520                 525             


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    530                 535                 540                 


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
545                 550                 555                 560 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                565                 570                 575     


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
            580                 585                 590         


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
        595                 600                 605             


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    610                 615                 620                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
625                 630                 635                 640 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                645                 650                 655     


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
            660                 665                 670         


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        675                 680                 685             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    690                 695                 700             


<210>  3
<211>  963
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide

<400>  3

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Val Ser Leu Gly Glu Arg Ala Thr Ile Ser Cys Lys Ser Ser Gln Ser 
        35                  40                  45              


Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln 
    50                  55                  60                  


Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg 
65                  70                  75                  80  


Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr 
            100                 105                 110         


Tyr Cys Gln Asn Asp Tyr Phe Tyr Pro Phe Thr Phe Gly Gln Gly Thr 
        115                 120                 125             


Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 
    130                 135                 140                 


Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 
145                 150                 155                 160 


Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 
                165                 170                 175     


Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 
            180                 185                 190         


Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 
        195                 200                 205             


Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 
    210                 215                 220                 


Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235                 240 


Gly Ser Ser Gly Arg Ser Glu Asn Ile Arg Thr Ala Gly Gly Ser Gln 
                245                 250                 255     


Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser 
            260                 265                 270         


Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Asn Tyr Leu 
        275                 280                 285             


Ile Glu Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly 
    290                 295                 300                 


Leu Ile Asn Pro Gly Ser Gly Gly Thr Asn Tyr Asn Glu Lys Phe Lys 
305                 310                 315                 320 


Gly Lys Ala Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met 
                325                 330                 335     


Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
            340                 345                 350         


Arg Val Tyr Tyr Gly Asn Ser Phe Ala Tyr Trp Gly Gln Gly Thr Leu 
        355                 360                 365             


Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
    370                 375                 380                 


Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
385                 390                 395                 400 


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


Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
            420                 425                 430         


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
        435                 440                 445             


Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
    450                 455                 460                 


Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
465                 470                 475                 480 


Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val 
                485                 490                 495     


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
            500                 505                 510         


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
        515                 520                 525             


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    530                 535                 540                 


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
545                 550                 555                 560 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                565                 570                 575     


Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile 
            580                 585                 590         


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
        595                 600                 605             


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    610                 615                 620                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
625                 630                 635                 640 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                645                 650                 655     


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
            660                 665                 670         


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        675                 680                 685             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
    690                 695                 700                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
705                 710                 715                 720 


Gly Gly Ser Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala 
                725                 730                 735     


Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val 
            740                 745                 750         


Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg 
        755                 760                 765             


Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro Ala His Phe 
    770                 775                 780                 


Arg Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Gly Met 
785                 790                 795                 800 


Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn 
                805                 810                 815     


Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Asn Gly Gly Gly 
            820                 825                 830         


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu 
        835                 840                 845             


Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala Ser Val Lys Met 
    850                 855                 860                 


Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Tyr Thr Met His Trp 
865                 870                 875                 880 


Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Tyr Ile Asn 
                885                 890                 895     


Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe Lys Asp Lys Ala 
            900                 905                 910         


Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser 
        915                 920                 925             


Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala Arg Tyr Tyr 
    930                 935                 940                 


Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr 
945                 950                 955                 960 


Val Ser Ser 
            


