                         SEQUENCE LISTING

<110>  3B Pharmaceuticals GmbH
 
<120>  Compounds comprising a fibroblast activation protein ligand and 
       use thereof

<130>  D 10026 PCT

<150>  EP 19 000 325.1
<151>  2019-07-08

<150>  EP 19 198 813.8
<151>  2019-09-20

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  760
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Fibroblast activation protein (FAP)

<400>  1

Met Lys Thr Trp Val Lys Ile Val Phe Gly Val Ala Thr Ser Ala Val 
1               5                   10                  15      


Leu Ala Leu Leu Val Met Cys Ile Val Leu Arg Pro Ser Arg Val His 
            20                  25                  30          


Asn Ser Glu Glu Asn Thr Met Arg Ala Leu Thr Leu Lys Asp Ile Leu 
        35                  40                  45              


Asn Gly Thr Phe Ser Tyr Lys Thr Phe Phe Pro Asn Trp Ile Ser Gly 
    50                  55                  60                  


Gln Glu Tyr Leu His Gln Ser Ala Asp Asn Asn Ile Val Leu Tyr Asn 
65                  70                  75                  80  


Ile Glu Thr Gly Gln Ser Tyr Thr Ile Leu Ser Asn Arg Thr Met Lys 
                85                  90                  95      


Ser Val Asn Ala Ser Asn Tyr Gly Leu Ser Pro Asp Arg Gln Phe Val 
            100                 105                 110         


Tyr Leu Glu Ser Asp Tyr Ser Lys Leu Trp Arg Tyr Ser Tyr Thr Ala 
        115                 120                 125             


Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn Gly Glu Phe Val Arg Gly Asn 
    130                 135                 140                 


Glu Leu Pro Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser 
145                 150                 155                 160 


Lys Leu Ala Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro 
                165                 170                 175     


Gly Asp Pro Pro Phe Gln Ile Thr Phe Asn Gly Arg Glu Asn Lys Ile 
            180                 185                 190         


Phe Asn Gly Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr 
        195                 200                 205             


Lys Tyr Ala Leu Trp Trp Ser Pro Asn Gly Lys Phe Leu Ala Tyr Ala 
    210                 215                 220                 


Glu Phe Asn Asp Thr Asp Ile Pro Val Ile Ala Tyr Ser Tyr Tyr Gly 
225                 230                 235                 240 


Asp Glu Gln Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly 
                245                 250                 255     


Ala Lys Asn Pro Val Val Arg Ile Phe Ile Ile Asp Thr Thr Tyr Pro 
            260                 265                 270         


Ala Tyr Val Gly Pro Gln Glu Val Pro Val Pro Ala Met Ile Ala Ser 
        275                 280                 285             


Ser Asp Tyr Tyr Phe Ser Trp Leu Thr Trp Val Thr Asp Glu Arg Val 
    290                 295                 300                 


Cys Leu Gln Trp Leu Lys Arg Val Gln Asn Val Ser Val Leu Ser Ile 
305                 310                 315                 320 


Cys Asp Phe Arg Glu Asp Trp Gln Thr Trp Asp Cys Pro Lys Thr Gln 
                325                 330                 335     


Glu His Ile Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val 
            340                 345                 350         


Ser Thr Pro Val Phe Ser Tyr Asp Ala Ile Ser Tyr Tyr Lys Ile Phe 
        355                 360                 365             


Ser Asp Lys Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Thr Val 
    370                 375                 380                 


Glu Asn Ala Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Asn Ile 
385                 390                 395                 400 


Phe Arg Val Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu 
                405                 410                 415     


Glu Tyr Pro Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Ser Tyr 
            420                 425                 430         


Pro Pro Ser Lys Lys Cys Val Thr Cys His Leu Arg Lys Glu Arg Cys 
        435                 440                 445             


Gln Tyr Tyr Thr Ala Ser Phe Ser Asp Tyr Ala Lys Tyr Tyr Ala Leu 
    450                 455                 460                 


Val Cys Tyr Gly Pro Gly Ile Pro Ile Ser Thr Leu His Asp Gly Arg 
465                 470                 475                 480 


Thr Asp Gln Glu Ile Lys Ile Leu Glu Glu Asn Lys Glu Leu Glu Asn 
                485                 490                 495     


Ala Leu Lys Asn Ile Gln Leu Pro Lys Glu Glu Ile Lys Lys Leu Glu 
            500                 505                 510         


Val Asp Glu Ile Thr Leu Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe 
        515                 520                 525             


Asp Arg Ser Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro 
    530                 535                 540                 


Cys Ser Gln Ser Val Arg Ser Val Phe Ala Val Asn Trp Ile Ser Tyr 
545                 550                 555                 560 


Leu Ala Ser Lys Glu Gly Met Val Ile Ala Leu Val Asp Gly Arg Gly 
                565                 570                 575     


Thr Ala Phe Gln Gly Asp Lys Leu Leu Tyr Ala Val Tyr Arg Lys Leu 
            580                 585                 590         


Gly Val Tyr Glu Val Glu Asp Gln Ile Thr Ala Val Arg Lys Phe Ile 
        595                 600                 605             


Glu Met Gly Phe Ile Asp Glu Lys Arg Ile Ala Ile Trp Gly Trp Ser 
    610                 615                 620                 


Tyr Gly Gly Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu 
625                 630                 635                 640 


Phe Lys Cys Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr 
                645                 650                 655     


Ala Ser Val Tyr Thr Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp 
            660                 665                 670         


Asn Leu Glu His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr 
        675                 680                 685             


Phe Arg Asn Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn 
    690                 695                 700                 


Val His Phe Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala 
705                 710                 715                 720 


Gln Val Asp Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Leu 
                725                 730                 735     


Ser Gly Leu Ser Thr Asn His Leu Tyr Thr His Met Thr His Phe Leu 
            740                 745                 750         


Lys Gln Cys Phe Ser Leu Ser Asp 
        755                 760 


<210>  2
<211>  766
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Dipeptidyl peptidase 4 (DPP4)

<400>  2

Met Lys Thr Pro Trp Lys Val Leu Leu Gly Leu Leu Gly Ala Ala Ala 
1               5                   10                  15      


Leu Val Thr Ile Ile Thr Val Pro Val Val Leu Leu Asn Lys Gly Thr 
            20                  25                  30          


Asp Asp Ala Thr Ala Asp Ser Arg Lys Thr Tyr Thr Leu Thr Asp Tyr 
        35                  40                  45              


Leu Lys Asn Thr Tyr Arg Leu Lys Leu Tyr Ser Leu Arg Trp Ile Ser 
    50                  55                  60                  


Asp His Glu Tyr Leu Tyr Lys Gln Glu Asn Asn Ile Leu Val Phe Asn 
65                  70                  75                  80  


Ala Glu Tyr Gly Asn Ser Ser Val Phe Leu Glu Asn Ser Thr Phe Asp 
                85                  90                  95      


Glu Phe Gly His Ser Ile Asn Asp Tyr Ser Ile Ser Pro Asp Gly Gln 
            100                 105                 110         


Phe Ile Leu Leu Glu Tyr Asn Tyr Val Lys Gln Trp Arg His Ser Tyr 
        115                 120                 125             


Thr Ala Ser Tyr Asp Ile Tyr Asp Leu Asn Lys Arg Gln Leu Ile Thr 
    130                 135                 140                 


Glu Glu Arg Ile Pro Asn Asn Thr Gln Trp Val Thr Trp Ser Pro Val 
145                 150                 155                 160 


Gly His Lys Leu Ala Tyr Val Trp Asn Asn Asp Ile Tyr Val Lys Ile 
                165                 170                 175     


Glu Pro Asn Leu Pro Ser Tyr Arg Ile Thr Trp Thr Gly Lys Glu Asp 
            180                 185                 190         


Ile Ile Tyr Asn Gly Ile Thr Asp Trp Val Tyr Glu Glu Glu Val Phe 
        195                 200                 205             


Ser Ala Tyr Ser Ala Leu Trp Trp Ser Pro Asn Gly Thr Phe Leu Ala 
    210                 215                 220                 


Tyr Ala Gln Phe Asn Asp Thr Glu Val Pro Leu Ile Glu Tyr Ser Phe 
225                 230                 235                 240 


Tyr Ser Asp Glu Ser Leu Gln Tyr Pro Lys Thr Val Arg Val Pro Tyr 
                245                 250                 255     


Pro Lys Ala Gly Ala Val Asn Pro Thr Val Lys Phe Phe Val Val Asn 
            260                 265                 270         


Thr Asp Ser Leu Ser Ser Val Thr Asn Ala Thr Ser Ile Gln Ile Thr 
        275                 280                 285             


Ala Pro Ala Ser Met Leu Ile Gly Asp His Tyr Leu Cys Asp Val Thr 
    290                 295                 300                 


Trp Ala Thr Gln Glu Arg Ile Ser Leu Gln Trp Leu Arg Arg Ile Gln 
305                 310                 315                 320 


Asn Tyr Ser Val Met Asp Ile Cys Asp Tyr Asp Glu Ser Ser Gly Arg 
                325                 330                 335     


Trp Asn Cys Leu Val Ala Arg Gln His Ile Glu Met Ser Thr Thr Gly 
            340                 345                 350         


Trp Val Gly Arg Phe Arg Pro Ser Glu Pro His Phe Thr Leu Asp Gly 
        355                 360                 365             


Asn Ser Phe Tyr Lys Ile Ile Ser Asn Glu Glu Gly Tyr Arg His Ile 
    370                 375                 380                 


Cys Tyr Phe Gln Ile Asp Lys Lys Asp Cys Thr Phe Ile Thr Lys Gly 
385                 390                 395                 400 


Thr Trp Glu Val Ile Gly Ile Glu Ala Leu Thr Ser Asp Tyr Leu Tyr 
                405                 410                 415     


Tyr Ile Ser Asn Glu Tyr Lys Gly Met Pro Gly Gly Arg Asn Leu Tyr 
            420                 425                 430         


Lys Ile Gln Leu Ser Asp Tyr Thr Lys Val Thr Cys Leu Ser Cys Glu 
        435                 440                 445             


Leu Asn Pro Glu Arg Cys Gln Tyr Tyr Ser Val Ser Phe Ser Lys Glu 
    450                 455                 460                 


Ala Lys Tyr Tyr Gln Leu Arg Cys Ser Gly Pro Gly Leu Pro Leu Tyr 
465                 470                 475                 480 


Thr Leu His Ser Ser Val Asn Asp Lys Gly Leu Arg Val Leu Glu Asp 
                485                 490                 495     


Asn Ser Ala Leu Asp Lys Met Leu Gln Asn Val Gln Met Pro Ser Lys 
            500                 505                 510         


Lys Leu Asp Phe Ile Ile Leu Asn Glu Thr Lys Phe Trp Tyr Gln Met 
        515                 520                 525             


Ile Leu Pro Pro His Phe Asp Lys Ser Lys Lys Tyr Pro Leu Leu Leu 
    530                 535                 540                 


Asp Val Tyr Ala Gly Pro Cys Ser Gln Lys Ala Asp Thr Val Phe Arg 
545                 550                 555                 560 


Leu Asn Trp Ala Thr Tyr Leu Ala Ser Thr Glu Asn Ile Ile Val Ala 
                565                 570                 575     


Ser Phe Asp Gly Arg Gly Ser Gly Tyr Gln Gly Asp Lys Ile Met His 
            580                 585                 590         


Ala Ile Asn Arg Arg Leu Gly Thr Phe Glu Val Glu Asp Gln Ile Glu 
        595                 600                 605             


Ala Ala Arg Gln Phe Ser Lys Met Gly Phe Val Asp Asn Lys Arg Ile 
    610                 615                 620                 


Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Thr Ser Met Val Leu 
625                 630                 635                 640 


Gly Ser Gly Ser Gly Val Phe Lys Cys Gly Ile Ala Val Ala Pro Val 
                645                 650                 655     


Ser Arg Trp Glu Tyr Tyr Asp Ser Val Tyr Thr Glu Arg Tyr Met Gly 
            660                 665                 670         


Leu Pro Thr Pro Glu Asp Asn Leu Asp His Tyr Arg Asn Ser Thr Val 
        675                 680                 685             


Met Ser Arg Ala Glu Asn Phe Lys Gln Val Glu Tyr Leu Leu Ile His 
    690                 695                 700                 


Gly Thr Ala Asp Asp Asn Val His Phe Gln Gln Ser Ala Gln Ile Ser 
705                 710                 715                 720 


Lys Ala Leu Val Asp Val Gly Val Asp Phe Gln Ala Met Trp Tyr Thr 
                725                 730                 735     


Asp Glu Asp His Gly Ile Ala Ser Ser Thr Ala His Gln His Ile Tyr 
            740                 745                 750         


Thr His Met Ser His Phe Ile Lys Gln Cys Phe Ser Leu Pro 
        755                 760                 765     


<210>  3
<211>  710
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Prolyl endopeptidase (PREP)

<400>  3

Met Leu Ser Leu Gln Tyr Pro Asp Val Tyr Arg Asp Glu Thr Ala Val 
1               5                   10                  15      


Gln Asp Tyr His Gly His Lys Ile Cys Asp Pro Tyr Ala Trp Leu Glu 
            20                  25                  30          


Asp Pro Asp Ser Glu Gln Thr Lys Ala Phe Val Glu Ala Gln Asn Lys 
        35                  40                  45              


Ile Thr Val Pro Phe Leu Glu Gln Cys Pro Ile Arg Gly Leu Tyr Lys 
    50                  55                  60                  


Glu Arg Met Thr Glu Leu Tyr Asp Tyr Pro Lys Tyr Ser Cys His Phe 
65                  70                  75                  80  


Lys Lys Gly Lys Arg Tyr Phe Tyr Phe Tyr Asn Thr Gly Leu Gln Asn 
                85                  90                  95      


Gln Arg Val Leu Tyr Val Gln Asp Ser Leu Glu Gly Glu Ala Arg Val 
            100                 105                 110         


Phe Leu Asp Pro Asn Ile Leu Ser Asp Asp Gly Thr Val Ala Leu Arg 
        115                 120                 125             


Gly Tyr Ala Phe Ser Glu Asp Gly Glu Tyr Phe Ala Tyr Gly Leu Ser 
    130                 135                 140                 


Ala Ser Gly Ser Asp Trp Val Thr Ile Lys Phe Met Lys Val Asp Gly 
145                 150                 155                 160 


Ala Lys Glu Leu Pro Asp Val Leu Glu Arg Val Lys Phe Ser Cys Met 
                165                 170                 175     


Ala Trp Thr His Asp Gly Lys Gly Met Phe Tyr Asn Ser Tyr Pro Gln 
            180                 185                 190         


Gln Asp Gly Lys Ser Asp Gly Thr Glu Thr Ser Thr Asn Leu His Gln 
        195                 200                 205             


Lys Leu Tyr Tyr His Val Leu Gly Thr Asp Gln Ser Glu Asp Ile Leu 
    210                 215                 220                 


Cys Ala Glu Phe Pro Asp Glu Pro Lys Trp Met Gly Gly Ala Glu Leu 
225                 230                 235                 240 


Ser Asp Asp Gly Arg Tyr Val Leu Leu Ser Ile Arg Glu Gly Cys Asp 
                245                 250                 255     


Pro Val Asn Arg Leu Trp Tyr Cys Asp Leu Gln Gln Glu Ser Ser Gly 
            260                 265                 270         


Ile Ala Gly Ile Leu Lys Trp Val Lys Leu Ile Asp Asn Phe Glu Gly 
        275                 280                 285             


Glu Tyr Asp Tyr Val Thr Asn Glu Gly Thr Val Phe Thr Phe Lys Thr 
    290                 295                 300                 


Asn Arg Gln Ser Pro Asn Tyr Arg Val Ile Asn Ile Asp Phe Arg Asp 
305                 310                 315                 320 


Pro Glu Glu Ser Lys Trp Lys Val Leu Val Pro Glu His Glu Lys Asp 
                325                 330                 335     


Val Leu Glu Trp Ile Ala Cys Val Arg Ser Asn Phe Leu Val Leu Cys 
            340                 345                 350         


Tyr Leu His Asp Val Lys Asn Ile Leu Gln Leu His Asp Leu Thr Thr 
        355                 360                 365             


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


Tyr Ser Gly Gln Lys Lys Asp Thr Glu Ile Phe Tyr Gln Phe Thr Ser 
385                 390                 395                 400 


Phe Leu Ser Pro Gly Ile Ile Tyr His Cys Asp Leu Thr Lys Glu Glu 
                405                 410                 415     


Leu Glu Pro Arg Val Phe Arg Glu Val Thr Val Lys Gly Ile Asp Ala 
            420                 425                 430         


Ser Asp Tyr Gln Thr Val Gln Ile Phe Tyr Pro Ser Lys Asp Gly Thr 
        435                 440                 445             


Lys Ile Pro Met Phe Ile Val His Lys Lys Gly Ile Lys Leu Asp Gly 
    450                 455                 460                 


Ser His Pro Ala Phe Leu Tyr Gly Tyr Gly Gly Phe Asn Ile Ser Ile 
465                 470                 475                 480 


Thr Pro Asn Tyr Ser Val Ser Arg Leu Ile Phe Val Arg His Met Gly 
                485                 490                 495     


Gly Ile Leu Ala Val Ala Asn Ile Arg Gly Gly Gly Glu Tyr Gly Glu 
            500                 505                 510         


Thr Trp His Lys Gly Gly Ile Leu Ala Asn Lys Gln Asn Cys Phe Asp 
        515                 520                 525             


Asp Phe Gln Cys Ala Ala Glu Tyr Leu Ile Lys Glu Gly Tyr Thr Ser 
    530                 535                 540                 


Pro Lys Arg Leu Thr Ile Asn Gly Gly Ser Asn Gly Gly Leu Leu Val 
545                 550                 555                 560 


Ala Ala Cys Ala Asn Gln Arg Pro Asp Leu Phe Gly Cys Val Ile Ala 
                565                 570                 575     


Gln Val Gly Val Met Asp Met Leu Lys Phe His Lys Tyr Thr Ile Gly 
            580                 585                 590         


His Ala Trp Thr Thr Asp Tyr Gly Cys Ser Asp Ser Lys Gln His Phe 
        595                 600                 605             


Glu Trp Leu Val Lys Tyr Ser Pro Leu His Asn Val Lys Leu Pro Glu 
    610                 615                 620                 


Ala Asp Asp Ile Gln Tyr Pro Ser Met Leu Leu Leu Thr Ala Asp His 
625                 630                 635                 640 


Asp Asp Arg Val Val Pro Leu His Ser Leu Lys Phe Ile Ala Thr Leu 
                645                 650                 655     


Gln Tyr Ile Val Gly Arg Ser Arg Lys Gln Ser Asn Pro Leu Leu Ile 
            660                 665                 670         


His Val Asp Thr Lys Ala Gly His Gly Ala Gly Lys Pro Thr Ala Lys 
        675                 680                 685             


Val Ile Glu Glu Val Ser Asp Met Phe Ala Phe Ile Ala Arg Cys Leu 
    690                 695                 700                 


Asn Val Asp Trp Ile Pro 
705                 710 


