                         SEQUENCE LISTING

<110>  PHILOGEN S.P.A
       DE LUCA, Roberto
       NADAL, Lisa
       PEISSERT, Frederik
 
<120>  ANTI-FIBROBLAST ACTIVATION PROTEIN ANTIBODIES

<130>  008229304

<140>  PCT/EP2022/060776
<141>  2022-04-22

<150>  EP21170280.8
<151>  2021-04-23

<150>  EP22159821.2
<151>  2022-03-02

<150>  EP21193852.7
<151>  2021-08-30

<150>  EP22150197.6
<151>  2022-01-04

<160>  85    

<170>  PatentIn version 3.5

<210>  1
<211>  735
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human extracellular domain of Fibroblast Activation Protein 
       (hFAP)

<400>  1

Leu Arg Pro Ser Arg Val His Asn Ser Glu Glu Asn Thr Met Arg Ala 
1               5                   10                  15      


Leu Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe Ser Tyr Lys Thr Phe 
            20                  25                  30          


Phe Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu His Gln Ser Ala Asp 
        35                  40                  45              


Asn Asn Ile Val Leu Tyr Asn Ile Glu Thr Gly Gln Ser Tyr Thr Ile 
    50                  55                  60                  


Leu Ser Asn Arg Thr Met Lys Ser Val Asn Ala Ser Asn Tyr Gly Leu 
65                  70                  75                  80  


Ser Pro Asp Arg Gln Phe Val Tyr Leu Glu Ser Asp Tyr Ser Lys Leu 
                85                  90                  95      


Trp Arg Tyr Ser Tyr Thr Ala Thr Tyr Tyr Ile Tyr Asp Leu Ser Asn 
            100                 105                 110         


Gly Glu Phe Val Arg Gly Asn Glu Leu Pro Arg Pro Ile Gln Tyr Leu 
        115                 120                 125             


Cys Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn 
    130                 135                 140                 


Ile Tyr Leu Lys Gln Arg Pro Gly Asp Pro Pro Phe Gln Ile Thr Phe 
145                 150                 155                 160 


Asn Gly Arg Glu Asn Lys Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr 
                165                 170                 175     


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


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


Ile Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln Tyr Pro Arg Thr Ile Asn 
    210                 215                 220                 


Ile Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Val Val Arg Ile Phe 
225                 230                 235                 240 


Ile Ile Asp Thr Thr Tyr Pro Ala Tyr Val Gly Pro Gln Glu Val Pro 
                245                 250                 255     


Val Pro Ala Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr 
            260                 265                 270         


Trp Val Thr Asp Glu Arg Val Cys Leu Gln Trp Leu Lys Arg Val Gln 
        275                 280                 285             


Asn Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Asp Trp Gln Thr 
    290                 295                 300                 


Trp Asp Cys Pro Lys Thr Gln Glu His Ile Glu Glu Ser Arg Thr Gly 
305                 310                 315                 320 


Trp Ala Gly Gly Phe Phe Val Ser Thr Pro Val Phe Ser Tyr Asp Ala 
                325                 330                 335     


Ile Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile 
            340                 345                 350         


His Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly 
        355                 360                 365             


Lys Trp Glu Ala Ile Asn Ile Phe Arg Val Thr Gln Asp Ser Leu Phe 
    370                 375                 380                 


Tyr Ser Ser Asn Glu Phe Glu Glu Tyr Pro Gly Arg Arg Asn Ile Tyr 
385                 390                 395                 400 


Arg Ile Ser Ile Gly Ser Tyr Pro Pro Ser Lys Lys Cys Val Thr Cys 
                405                 410                 415     


His Leu Arg Lys Glu Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Asp 
            420                 425                 430         


Tyr Ala Lys Tyr Tyr Ala Leu Val Cys Tyr Gly Pro Gly Ile Pro Ile 
        435                 440                 445             


Ser Thr Leu His Asp Gly Arg Thr Asp Gln Glu Ile Lys Ile Leu Glu 
    450                 455                 460                 


Glu Asn Lys Glu Leu Glu Asn Ala Leu Lys Asn Ile Gln Leu Pro Lys 
465                 470                 475                 480 


Glu Glu Ile Lys Lys Leu Glu Val Asp Glu Ile Thr Leu Trp Tyr Lys 
                485                 490                 495     


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


Ile Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Arg Ser Val Phe 
        515                 520                 525             


Ala Val Asn Trp Ile Ser Tyr Leu Ala Ser Lys Glu Gly Met Val Ile 
    530                 535                 540                 


Ala Leu Val Asp Gly Arg Gly Thr Ala Phe Gln Gly Asp Lys Leu Leu 
545                 550                 555                 560 


Tyr Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Ile 
                565                 570                 575     


Thr Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Lys Arg 
            580                 585                 590         


Ile Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala 
        595                 600                 605             


Leu Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro 
    610                 615                 620                 


Val Ser Ser Trp Glu Tyr Tyr Ala Ser Val Tyr Thr Glu Arg Phe Met 
625                 630                 635                 640 


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


Val Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile 
            660                 665                 670         


His Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile 
        675                 680                 685             


Ala Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr 
    690                 695                 700                 


Ser Asp Gln Asn His Gly Leu Ser Gly Leu Ser Thr Asn His Leu Tyr 
705                 710                 715                 720 


Thr His Met Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp 
                725                 730                 735 


<210>  2
<211>  735
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  canine extracellular domain of Fibroblast Activation Protein 
       (caFAP)

<400>  2

Leu Arg Pro Ser Arg Val His Asp Ser Glu Gly Gly Thr Thr Arg Ala 
1               5                   10                  15      


Leu Thr Leu Glu Asp Ile Leu Asn Gly Thr Phe Thr Tyr Lys Thr Phe 
            20                  25                  30          


Phe Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu His Gln Ser Thr Asp 
        35                  40                  45              


Asn Asp Ile Val Tyr Tyr Asn Ile Glu Thr Gly Glu Ser Tyr Thr Ile 
    50                  55                  60                  


Leu Ser Asn Ala Thr Met Lys Ser Val Asn Ala Ser Asn Tyr Gly Leu 
65                  70                  75                  80  


Ser Pro Asp Arg Gln Phe Ala Tyr Leu Glu Ser Asp Tyr Ser Lys Leu 
                85                  90                  95      


Trp Arg Tyr Ser Tyr Thr Ala Thr Tyr His Ile Tyr Asn Leu Asn Asn 
            100                 105                 110         


Gly Glu Phe Ile Arg Arg Asn Glu Leu Pro Arg Pro Ile Gln Tyr Leu 
        115                 120                 125             


Cys Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn 
    130                 135                 140                 


Ile Tyr Leu Lys Gln Arg Pro Glu Asp Pro Pro Phe Gln Ile Thr Tyr 
145                 150                 155                 160 


Asn Gly Arg Glu Asn Lys Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr 
                165                 170                 175     


Glu Glu Glu Met Leu Ala Thr Lys His Ala Leu Trp Trp Ser Pro Asn 
            180                 185                 190         


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


Ile Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln Tyr Pro Arg Thr Ile Asn 
    210                 215                 220                 


Ile Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Val Val Arg Ile Phe 
225                 230                 235                 240 


Ile Ile Asp Thr Thr Tyr Pro Gln Gln Thr Gly Pro Arg Glu Val Pro 
                245                 250                 255     


Val Pro Ala Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr 
            260                 265                 270         


Trp Val Thr Asp Glu Arg Val Cys Leu Gln Trp Leu Lys Arg Ile Gln 
        275                 280                 285             


Asn Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Gly Trp Gln Thr 
    290                 295                 300                 


Trp Asp Cys Pro Lys Ala Gln Glu His Ile Glu Glu Ser Arg Thr Gly 
305                 310                 315                 320 


Trp Ala Gly Gly Phe Phe Val Ser Thr Pro Val Phe Ser Tyr Asp Ala 
                325                 330                 335     


Ile Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile 
            340                 345                 350         


His Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly 
        355                 360                 365             


Lys Trp Glu Ala Ile Asn Ile Phe Arg Val Thr Gln Asp Ser Leu Phe 
    370                 375                 380                 


Tyr Ser Ser Asn Glu Phe Glu Asp Tyr Pro Gly Arg Arg Asn Ile Tyr 
385                 390                 395                 400 


Arg Ile Ser Ile Gly Ser Ser Pro Pro Ser Lys Lys Cys Ile Thr Cys 
                405                 410                 415     


His Leu Arg Lys Glu Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Asp 
            420                 425                 430         


Tyr Ala Lys Tyr Tyr Ala Leu Ile Cys Tyr Gly Pro Gly Leu Pro Ile 
        435                 440                 445             


Ser Thr Leu His Asp Gly His Thr Asp Gln Glu Ile Lys Ile Leu Glu 
    450                 455                 460                 


Glu Asn Lys Glu Leu Glu Asn Ala Leu Lys Asn Ile Gln Leu Pro Lys 
465                 470                 475                 480 


Glu Glu Ile Lys Lys Leu Glu Val Asp Asp Ile Thr Leu Trp Tyr Lys 
                485                 490                 495     


Met Met Leu Pro Pro Arg Phe Asp Arg Ser Lys Lys Tyr Pro Leu Leu 
            500                 505                 510         


Ile Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Lys Ser Val Phe 
        515                 520                 525             


Ser Ile Asn Trp Ile Ser Tyr Leu Ala Ser Lys Glu Gly Ile Val Ile 
    530                 535                 540                 


Ala Leu Val Asp Gly Arg Gly Thr Ala Tyr Gln Gly Asp Lys Leu Leu 
545                 550                 555                 560 


Tyr Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Ile 
                565                 570                 575     


Thr Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Lys Arg 
            580                 585                 590         


Ile Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala 
        595                 600                 605             


Leu Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro 
    610                 615                 620                 


Val Ser Ser Trp Glu Tyr Tyr Ala Ser Ile Tyr Thr Glu Arg Phe Met 
625                 630                 635                 640 


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


Val Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile 
            660                 665                 670         


His Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile 
        675                 680                 685             


Ala Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr 
    690                 695                 700                 


Ser Asp Gln Asn His Gly Ile Pro Gly Leu Ser Ser Lys His Leu Tyr 
705                 710                 715                 720 


Thr Arg Met Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp 
                725                 730                 735 


<210>  3
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 CDR1 VH

<400>  3

Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser 
1               5                   10  


<210>  4
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 CDR2 VH

<400>  4

Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  7NP2 CDR3 VH

<400>  5

Arg Leu Ala Trp Phe Asp Tyr 
1               5           


<210>  6
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 CDR1 VL

<400>  6

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 
1               5                   10          


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

<220>
<223>  7NP2 CDR2 VL

<400>  7

Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210>  8
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 CDR3 VL

<400>  8

Gln Gln Ser Gly Lys Gly Pro Leu Thr 
1               5                   


<210>  9
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 VH domain

<400>  9

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  10
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 VL domain

<400>  10

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro 
                85                  90                  95      


Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             


<210>  11
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 antibody molecule in scFv format

<400>  11

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             


Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 
    130                 135                 140                 


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


Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 
                165                 170                 175     


Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 
        195                 200                 205             


Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys 
    210                 215                 220                 


Gly Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
225                 230                 235             


<210>  12
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker between VH and VL in 7NP2 scFv and C5 scFv

<400>  12

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   10                  


<210>  13
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 heavy chain in IgG1 format

<400>  13

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
    210                 215                 220                 


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 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 Asp Glu Leu 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>  14
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 light chain in IgG (e.g. IgG1) format

<400>  14

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro 
                85                  90                  95      


Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 
            100                 105                 110         


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


Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         


Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             


Ser Phe Asn Arg Gly Glu Cys 
    210                 215 


<210>  15
<211>  359
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 antibody molecule in SIP format

<400>  15

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             


Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 
    130                 135                 140                 


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


Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 
                165                 170                 175     


Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 
        195                 200                 205             


Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys 
    210                 215                 220                 


Gly Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Gly 
225                 230                 235                 240 


Gly Ser Gly Gly Pro Arg Ala Ala Pro Glu Val Tyr Ala Phe Ala Thr 
                245                 250                 255     


Pro Glu Trp Pro Gly Ser Arg Asp Lys Arg Thr Leu Ala Cys Leu Ile 
            260                 265                 270         


Gln Asn Phe Met Pro Glu Asp Ile Ser Val Gln Trp Leu His Asn Glu 
        275                 280                 285             


Val Gln Leu Pro Asp Ala Arg His Ser Thr Thr Gln Pro Arg Lys Thr 
    290                 295                 300                 


Lys Gly Ser Gly Phe Phe Val Phe Ser Arg Leu Glu Val Thr Arg Ala 
305                 310                 315                 320 


Glu Trp Glu Gln Lys Asp Glu Phe Ile Cys Arg Ala Val His Glu Ala 
                325                 330                 335     


Ala Ser Pro Ser Gln Thr Val Gln Arg Ala Val Ser Val Asn Pro Glu 
            340                 345                 350         


Ser Ser Arg Arg Gly Gly Cys 
        355                 


<210>  16
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker between scFv and epsilon S2_CH4 domain in the SIP format

<400>  16

Ser Gly Gly Ser Gly Gly 
1               5       


<210>  17
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 CDR1 VH

<400>  17

Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser 
1               5                   10  


<210>  18
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 CDR2 VH

<400>  18

Ala Ile Asp Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  19
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 CDR3 VH

<400>  19

Arg Leu Ala Trp Phe Asp Tyr 
1               5           


<210>  20
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 CDR1 VL

<400>  20

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 
1               5                   10          


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

<220>
<223>  C5 CDR2 VL

<400>  21

Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210>  22
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 CDR3 VL

<400>  22

Gln Gln Ser Gly Lys Gly Pro Leu Thr 
1               5                   


<210>  23
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 VH domain

<400>  23

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Asp Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  24
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 VL domain

<400>  24

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro 
                85                  90                  95      


Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             


<210>  25
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 antibody molecule in scFv format

<400>  25

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Asp Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             


Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 
    130                 135                 140                 


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


Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 
                165                 170                 175     


Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 
        195                 200                 205             


Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys 
    210                 215                 220                 


Gly Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
225                 230                 235             


<210>  26
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 heavy chain in murine IgG2a format

<400>  26

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Asp Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala 
        115                 120                 125             


Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly 
145                 150                 155                 160 


Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp 
                165                 170                 175     


Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro 
            180                 185                 190         


Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys 
        195                 200                 205             


Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro 
    210                 215                 220                 


Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe 
225                 230                 235                 240 


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


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


Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr 
        275                 280                 285             


Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala 
    290                 295                 300                 


Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys 
305                 310                 315                 320 


Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser 
                325                 330                 335     


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


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


Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly 
    370                 375                 380                 


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


Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp 
                405                 410                 415     


Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His 
            420                 425                 430         


Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 
        435                 440                 445     


<210>  27
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C5 light chain in murine IgG2a format

<400>  27

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro 
                85                  90                  95      


Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Asp Ala 
            100                 105                 110         


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


Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp 
    130                 135                 140                 


Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val 
145                 150                 155                 160 


Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met 
                165                 170                 175     


Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser 
            180                 185                 190         


Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys 
        195                 200                 205             


Ser Phe Asn Arg Asn Glu Cys 
    210                 215 


<210>  28
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  KSF heavy chain in IgG1 format

<400>  28

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Pro Lys Val Ser Leu Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     


Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
            180                 185                 190         


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 
    210                 215                 220                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 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 His Glu Asp Pro 
            260                 265                 270         


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


Lys Thr Lys Pro Arg Glu Glu Gln Tyr 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 Ala Leu Pro Ala Pro 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 Arg Asp Glu Leu 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 Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     


Arg Trp Gln Gln 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 Pro Gly Lys 
        435                 440                 445             


<210>  29
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  KSF light chain in IgG1 format

<400>  29

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


Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


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


Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser 
    50                  55                  60                  


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Ser Pro Leu Asn Arg Leu Ala 
                85                  90                  95      


Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys 
            100                 105                 110         


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


Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly 
    130                 135                 140                 


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


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


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


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


Ala Pro Thr Glu Cys Ser 
    210                 


<210>  30
<211>  362
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  KSF antibody molecule in SIP format

<400>  30

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Pro Lys Val Ser Leu Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val 
    130                 135                 140                 


Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg 
145                 150                 155                 160 


Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val 
                165                 170                 175     


Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly 
        195                 200                 205             


Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Ser Pro Leu 
    210                 215                 220                 


Asn Arg Leu Ala Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
225                 230                 235                 240 


Gly Ser Gly Gly Ser Gly Gly Pro Arg Ala Ala Pro Glu Val Tyr Ala 
                245                 250                 255     


Phe Ala Thr Pro Glu Trp Pro Gly Ser Arg Asp Lys Arg Thr Leu Ala 
            260                 265                 270         


Cys Leu Ile Gln Asn Phe Met Pro Glu Asp Ile Ser Val Gln Trp Leu 
        275                 280                 285             


His Asn Glu Val Gln Leu Pro Asp Ala Arg His Ser Thr Thr Gln Pro 
    290                 295                 300                 


Arg Lys Thr Lys Gly Ser Gly Phe Phe Val Phe Ser Arg Leu Glu Val 
305                 310                 315                 320 


Thr Arg Ala Glu Trp Glu Gln Lys Asp Glu Phe Ile Cys Arg Ala Val 
                325                 330                 335     


His Glu Ala Ala Ser Pro Ser Gln Thr Val Gln Arg Ala Val Ser Val 
            340                 345                 350         


Asn Pro Glu Ser Ser Arg Arg Gly Gly Cys 
        355                 360         


<210>  31
<211>  555
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL2-7NP2-TNF alpha mut conjugate

<400>  31

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His 
1               5                   10                  15      


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala 
    130                 135                 140                 


Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
145                 150                 155                 160 


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser 
                165                 170                 175     


Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
            180                 185                 190         


Val Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser 
        195                 200                 205             


Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 
    210                 215                 220                 


Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 
225                 230                 235                 240 


Cys Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                245                 250                 255     


Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
            260                 265                 270         


Gly Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu 
        275                 280                 285             


Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val 
    290                 295                 300                 


Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
305                 310                 315                 320 


Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp 
                325                 330                 335     


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
            340                 345                 350         


Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly 
        355                 360                 365             


Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser 
    370                 375                 380                 


Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Val Arg 
385                 390                 395                 400 


Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala 
                405                 410                 415     


Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Ala Ala Asn 
            420                 425                 430         


Ala Leu Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val 
        435                 440                 445             


Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly 
    450                 455                 460                 


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


Ile Ala Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys 
                485                 490                 495     


Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp 
            500                 505                 510         


Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp 
        515                 520                 525             


Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu 
    530                 535                 540                 


Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala Leu 
545                 550                 555 


<210>  32
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker between IL2 and 7NP2

<400>  32

Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala Ser 
1               5                   10          


<210>  33
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker between 7NP2 and TNF alpha mut

<400>  33

Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
1               5                   10                  15  


<210>  34
<211>  133
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human Interleukin 2 (IL2)

<400>  34

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His 
1               5                   10                  15      


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr 
    130             


<210>  35
<211>  157
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Soluble form of the extracellular domain of human TNFalpha (R32A)
       mutant

<400>  35

Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val 
1               5                   10                  15      


Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Ala 
            20                  25                  30          


Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu 
        35                  40                  45              


Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe 
    50                  55                  60                  


Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile 
65                  70                  75                  80  


Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala 
                85                  90                  95      


Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys 
            100                 105                 110         


Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys 
        115                 120                 125             


Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe 
    130                 135                 140                 


Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala Leu 
145                 150                 155         


<210>  36
<211>  558
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL2-KSF-TNFalpha mut conjugate

<400>  36

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His 
1               5                   10                  15      


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala 
    130                 135                 140                 


Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
145                 150                 155                 160 


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser 
                165                 170                 175     


Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
            180                 185                 190         


Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser 
        195                 200                 205             


Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 
    210                 215                 220                 


Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 
225                 230                 235                 240 


Cys Ala Lys Ser Pro Lys Val Ser Leu Phe Asp Tyr Trp Gly Gln Gly 
                245                 250                 255     


Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            260                 265                 270         


Ser Gly Gly Gly Gly Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser 
        275                 280                 285             


Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu 
    290                 295                 300                 


Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
305                 310                 315                 320 


Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp 
                325                 330                 335     


Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr 
            340                 345                 350         


Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Ser Pro 
        355                 360                 365             


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


Leu Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser 
385                 390                 395                 400 


Gly Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His 
                405                 410                 415     


Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg 
            420                 425                 430         


Ala Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln 
        435                 440                 445             


Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu 
    450                 455                 460                 


Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu Thr His Thr 
465                 470                 475                 480 


Ile Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser 
                485                 490                 495     


Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala 
            500                 505                 510         


Lys Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu 
        515                 520                 525             


Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp 
    530                 535                 540                 


Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala Leu 
545                 550                 555             


<210>  37
<211>  574
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 Heavy chain IgG4-INF gamma  Mut KRG conjugate

<400>  37

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


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


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


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


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


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


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


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


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


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


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


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


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Ser Gln Asp Pro Tyr 
        435                 440                 445             


Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser 
    450                 455                 460                 


Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp 
465                 470                 475                 480 


Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe 
                485                 490                 495     


Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys 
            500                 505                 510         


Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser 
        515                 520                 525             


Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val 
    530                 535                 540                 


Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val 
545                 550                 555                 560 


Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Gly 
                565                 570                 


<210>  38
<211>  229
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 antibody in diabody format (Db)

<400>  38

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val Leu Thr Gln Ser 
        115                 120                 125             


Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 
    130                 135                 140                 


Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 
145                 150                 155                 160 


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 
                165                 170                 175     


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            180                 185                 190         


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 
        195                 200                 205             


Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr 
    210                 215                 220                 


Lys Val Glu Ile Lys 
225                 


<210>  39
<211>  473
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 antibody in single-chain diabody format (scDb)

<400>  39

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val Leu Thr Gln Ser 
        115                 120                 125             


Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 
    130                 135                 140                 


Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 
145                 150                 155                 160 


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 
                165                 170                 175     


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            180                 185                 190         


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 
        195                 200                 205             


Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr 
    210                 215                 220                 


Lys Val Glu Ile Lys Asp Ile Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


Gly Gly Gly Gly Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 
                245                 250                 255     


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 
            260                 265                 270         


Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
        275                 280                 285             


Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr 
    290                 295                 300                 


Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
305                 310                 315                 320 


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
                325                 330                 335     


Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln 
            340                 345                 350         


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val 
        355                 360                 365             


Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 
    370                 375                 380                 


Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 
385                 390                 395                 400 


Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 
                405                 410                 415     


Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 
            420                 425                 430         


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


Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe 
    450                 455                 460                 


Gly Gln Gly Thr Lys Val Glu Ile Lys 
465                 470             


<210>  40
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker between VH and VL in the 7NP2 Db and 7NP2 scDb

<400>  40

Gly Gly Ser Gly Gly 
1               5   


<210>  41
<211>  1006
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL12-7NP2 conjugate

<400>  41

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu 
    530                 535                 540                 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
545                 550                 555                 560 


Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
                565                 570                 575     


Gly Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr 
            580                 585                 590         


Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
        595                 600                 605             


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
    610                 615                 620                 


Ala Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly 
625                 630                 635                 640 


Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile 
                645                 650                 655     


Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg 
            660                 665                 670         


Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu 
        675                 680                 685             


Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 
    690                 695                 700                 


Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 
705                 710                 715                 720 


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 
                725                 730                 735     


Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr 
            740                 745                 750         


Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Asp Ile Gly Gly Gly Ser 
        755                 760                 765             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Glu Val Gln Leu Leu Glu Ser 
    770                 775                 780                 


Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala 
785                 790                 795                 800 


Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln 
                805                 810                 815     


Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly 
            820                 825                 830         


Gly Pro Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser 
        835                 840                 845             


Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg 
    850                 855                 860                 


Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe 
865                 870                 875                 880 


Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser 
                885                 890                 895     


Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser 
            900                 905                 910         


Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser 
        915                 920                 925             


Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 
    930                 935                 940                 


Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg 
945                 950                 955                 960 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 
                965                 970                 975     


Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys 
            980                 985                 990         


Gly Pro Leu Thr Phe Gly Gln Gly  Thr Lys Val Glu Ile  Lys 
        995                 1000                 1005     


<210>  42
<211>  65
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "Leader Seq DP47" > primer

<400>  42
tcctcctgtt cctcgtcgct gtggctacag gtgtgcactc ggaggtgcag ctgttggagt       60

ctggg                                                                   65


<210>  43
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "HindIII Stop Myc" < primer

<400>  43
tcgataagct tttatgcggc cccattcaga tcctcttc                               38


<210>  44
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "NheI_leader" > primer

<400>  44
ctagctagcg tcgaccatgg gctggagcct gatcctcctg ttcctcgtcg ctgtggc          57


<210>  45
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "Lmb3long" > primer

<400>  45
caggaaacag ctatgaccat gattac                                            26


<210>  46
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DP47 rCDR2" < primer


<220>
<221>  misc_feature
<222>  (29)..(30)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (38)..(39)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (41)..(42)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (44)..(45)
<223>  n is a, c, g, or t

<400>  46
gcccttcacg gagtctgcgt agtatgtmnn accaccmnnm nnmnn                       45


<210>  47
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DP47 CDR2" > primer

<400>  47
acatactacg cagactccgt gaagggc                                           27


<210>  48
<211>  42
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DPK22 rCDR2" < primer


<220>
<221>  misc_feature
<222>  (23)..(24)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (29)..(30)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (38)..(39)
<223>  n is a, c, g, or t

<400>  48
gaacctgtct gggatgccag tmnncctmnn ggatgcmnna ta                          42


<210>  49
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DPK22 rCDR2" > primer

<400>  49
actggcatcc cagacaggtt cagtg                                             25


<210>  50
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "Fdseqlong" < primer

<400>  50
gacgttagta aatgaatttt ctgtatgagg                                        30


<210>  51
<211>  67
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "086_LC22_1PCR"> primer

<400>  51
tcctcctgtt cctcgtcgct gtggctacag gtgtgcactc ggaaattgtg ttgacgcagt       60

ctccagg                                                                 67


<210>  52
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DPK22_BsiWI" <  primer

<400>  52
gcagccaccg tacgtttgat ttccaccttg gtcccttg                               38


<210>  53
<211>  58
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "063-L19-LC-SF" > primer

<400>  53
attaactagt gtcgaccatg ggctggagcc tgatcctcct gttcctcgtc gctgtggc         58


<210>  54
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DP47_XhoI" < primer

<400>  54
tggtcgacgc actcgagacg gtgaccaggg t                                      31


<210>  55
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "061-L19-HC" > primer

<400>  55
attaaagctt gtcgaccatg ggctggagcc tgatcctcct gttcc                       45


<210>  56
<211>  49
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "CH4 DPK22" < primer

<400>  56
cacgcgggcc cccagagcct ccggatttga tttccacctt ggtcccttg                   49


<210>  57
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "CH4" > primer

<400>  57
tccggaggct ctgggggccc gcgtg                                             25


<210>  58
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "NOTI STOP CH4" < primer

<400>  58
ttttcctttt gcggccgcct agcagccacc cctcctcgat gactc                       45


<210>  59
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "caFAP_BamHI" < primer

<400>  59
cattctggat ccgtttgagc cactgaaggc acacgcgctc                             40


<210>  60
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "caFAP_BamHI" > primer

<400>  60
gctcaaacgg atccagaatg tgagtgtcct gtccatttgc                             40


<210>  61
<211>  49
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "NotI-STOP-HIS" < primer

<400>  61
tttccttttg cggccgctca ttaagctatc agtgatggtg atggtgatg                   49


<210>  62
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "Link-F8 VH" > primer

<400>  62
gctcttcagg cggctctggc ggagcttccg aggtgcagct gttggagt                    48


<210>  63
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "L19-SSG" < primer

<400>  63
cggaagagct actacccgat gaggaagatt tgatttccac cttggtcc                    48


<210>  64
<211>  47
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "hIL2-Li12aa" < primer

<400>  64
gccagagccg cctgaagagc cgtcaccagt cagtgttgag atgatgc                     47


<210>  65
<211>  55
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "link-hsTNF" > primer

<400>  65
cgggtagtag ctcttccggc tcatcgtcca gcggcgtcag atcatcttct cgaac            55


<210>  66
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "NotISTOP-hsTNF" < primer

<400>  66
tttccttttg cggccgctca ttaagctatc acagggcaat gatcccaaag                  50


<210>  67
<211>  62
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "085-LC16-1PCR" > primer

<400>  67
tcctcctgtt cctcgtcgct gtggctacag gtgtgcactc gtcgtctgag ctgactcagg       60

ac                                                                      62


<210>  68
<211>  42
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  "DPL16_HpaI" < primer

<400>  68
agggggcagc cttgggctgg cctaggacgg ttaacttggt cc                          42


<210>  69
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Flexible linker connecting the two sets of VH and VL domains in 
       the 7NP2 scDb

<400>  69

Asp Ile Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   10                  15  


<210>  70
<211>  518
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single-chain human IL12

<400>  70

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser 
        515             


<210>  71
<211>  130
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IFN gamma Mut

<400>  71

Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn 
1               5                   10                  15      


Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile 
            20                  25                  30          


Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln 
        35                  40                  45              


Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln 
    50                  55                  60                  


Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys 
65                  70                  75                  80  


Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr 
                85                  90                  95      


Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu 
            100                 105                 110         


Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys 
        115                 120                 125             


Arg Gly 
    130 


<210>  72
<211>  735
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  ovine extracellular domain of Fibroblast Activation Protein 
       (oFAP)

<400>  72

Leu Arg Pro Ser Arg Val His Asn Ser Glu Asp Ser Ala Thr Arg Ala 
1               5                   10                  15      


Leu Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe Ser Tyr Lys Thr Phe 
            20                  25                  30          


Phe Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu His Gln Ser Thr Asp 
        35                  40                  45              


Asn Asn Val Val Phe Tyr Asn Ile Glu Thr Gly Glu Ser Tyr Thr Ile 
    50                  55                  60                  


Leu Ser Asn Thr Thr Met Lys Ser Val Asn Ala Ser Asn Tyr Gly Leu 
65                  70                  75                  80  


Ser Pro Asp Arg Gln Phe Ala Tyr Leu Glu Ser Asp Tyr Ser Lys Leu 
                85                  90                  95      


Trp Arg Tyr Ser Tyr Thr Ala Thr Tyr His Ile Tyr Asp Leu Thr Asn 
            100                 105                 110         


Gly Glu Phe Ile Arg Arg Asn Glu Leu Pro Arg Pro Ile Gln Tyr Leu 
        115                 120                 125             


Cys Trp Ser Pro Val Gly Ser Lys Leu Ala Tyr Val Tyr Gln Asn Asn 
    130                 135                 140                 


Ile Tyr Leu Lys Gln Arg Pro Glu Asp Pro Pro Phe Gln Ile Thr Tyr 
145                 150                 155                 160 


Asn Gly Lys Glu Asn Lys Ile Phe Asn Gly Ile Pro Asp Trp Val Tyr 
                165                 170                 175     


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


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


Ile Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln Tyr Pro Arg Thr Ile Asn 
    210                 215                 220                 


Ile Pro Tyr Pro Lys Ala Gly Ala Lys Asn Pro Val Val Arg Ile Phe 
225                 230                 235                 240 


Ile Ile Asp Ala Thr Tyr Pro Glu His Ile Gly Pro Arg Glu Val Pro 
                245                 250                 255     


Val Pro Ala Met Ile Ala Ser Ser Asp Tyr Tyr Phe Ser Trp Leu Thr 
            260                 265                 270         


Trp Val Thr Asp Asp Arg Ile Cys Leu Gln Trp Leu Lys Arg Ile Gln 
        275                 280                 285             


Asn Val Ser Val Leu Ser Ile Cys Asp Phe Arg Glu Asp Trp His Thr 
    290                 295                 300                 


Trp Asn Cys Pro Lys Thr Gln Glu His Ile Glu Glu Ser Arg Thr Gly 
305                 310                 315                 320 


Trp Ala Gly Gly Phe Phe Val Ser Thr Pro Val Phe Ser His Asp Thr 
                325                 330                 335     


Ile Ser Tyr Tyr Lys Ile Phe Ser Asp Lys Asp Gly Tyr Lys His Ile 
            340                 345                 350         


His Tyr Ile Lys Asp Thr Val Glu Asn Ala Ile Gln Ile Thr Ser Gly 
        355                 360                 365             


Lys Trp Glu Ala Ile Asn Ile Phe Arg Val Thr Gln Asp Ser Leu Phe 
    370                 375                 380                 


Tyr Ser Ser Asn Glu Phe Glu Gly Tyr Pro Gly Arg Arg Asn Ile Tyr 
385                 390                 395                 400 


Arg Ile Ser Ile Gly Ser His Ser Pro Ser Lys Lys Cys Ile Thr Cys 
                405                 410                 415     


His Leu Arg Lys Lys Arg Cys Gln Tyr Tyr Thr Ala Ser Phe Ser Asp 
            420                 425                 430         


Tyr Ala Lys Tyr Tyr Ala Leu Val Cys Tyr Gly Pro Gly Leu Pro Ile 
        435                 440                 445             


Ser Thr Leu His Asp Gly Arg Thr Asp Gln Glu Ile Lys Ile Leu Glu 
    450                 455                 460                 


Asp Asn Lys Glu Leu Glu Asn Ala Leu Lys Asn Ile Gln Leu Pro Lys 
465                 470                 475                 480 


Glu Glu Ile Lys Lys Leu Lys Val Asp Asp Ile Thr Leu Trp Tyr Lys 
                485                 490                 495     


Met Ile Leu Pro Pro Gln Phe Asp Lys Ser Lys Lys Tyr Pro Leu Leu 
            500                 505                 510         


Ile Gln Val Tyr Gly Gly Pro Cys Ser Gln Ser Val Arg Ser Val Phe 
        515                 520                 525             


Ala Val Ser Trp Ile Ser Tyr Leu Ala Ser Lys Glu Gly Ile Val Ile 
    530                 535                 540                 


Ala Leu Val Asp Gly Arg Gly Thr Ala Phe Gln Gly Asp Arg Leu Leu 
545                 550                 555                 560 


Tyr Ala Val Tyr Arg Lys Leu Gly Val Tyr Glu Val Glu Asp Gln Ile 
                565                 570                 575     


Thr Ala Val Arg Lys Phe Ile Glu Met Gly Phe Ile Asp Glu Lys Arg 
            580                 585                 590         


Ile Ala Ile Trp Gly Trp Ser Tyr Gly Gly Tyr Val Ser Ser Leu Ala 
        595                 600                 605             


Leu Ala Ser Gly Thr Gly Leu Phe Lys Cys Gly Ile Ala Val Ala Pro 
    610                 615                 620                 


Val Ser Ser Trp Glu Tyr Tyr Ala Ser Ile Tyr Thr Glu Arg Phe Met 
625                 630                 635                 640 


Gly Leu Pro Thr Lys Asp Asp Asn Leu Lys His Tyr Lys Asn Ser Thr 
                645                 650                 655     


Val Met Ala Arg Ala Glu Tyr Phe Arg Asn Val Asp Tyr Leu Leu Ile 
            660                 665                 670         


His Gly Thr Ala Asp Asp Asn Val His Phe Gln Asn Ser Ala Gln Ile 
        675                 680                 685             


Ala Lys Ala Leu Val Asn Ala Gln Val Asp Phe Gln Ala Met Trp Tyr 
    690                 695                 700                 


Ser Asp Gln Asn His Gly Leu Ser Gly Leu Ser Thr Lys His Leu Tyr 
705                 710                 715                 720 


Ile His Ile Thr His Phe Leu Lys Gln Cys Phe Ser Leu Ser Asp 
                725                 730                 735 


<210>  73
<211>  709
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  porcine extracellular domain of Fibroblast Activation Protein 
       (pFAP)

<400>  73

Ile Lys Thr Arg Ala Leu Thr Leu Lys Asp Ile Leu Asn Gly Thr Phe 
1               5                   10                  15      


Ser Tyr Lys Thr Phe Phe Pro Asn Trp Ile Ser Gly Gln Glu Tyr Leu 
            20                  25                  30          


His Gln Ser Thr Asp Asp Asn Val Ile Phe Tyr Asn Ile Glu Thr Gly 
        35                  40                  45              


Glu Ser Tyr Thr Ile Leu Ser Asn Thr Thr Met Val Cys Ile Gln His 
    50                  55                  60                  


Cys Leu Pro Gln Lys Pro Leu Pro Phe Ile Tyr Leu Phe Ile Tyr Phe 
65                  70                  75                  80  


Leu Tyr Phe Phe Ser Ser Arg Glu Phe Ile Thr Arg Asn Glu Leu Pro 
                85                  90                  95      


Arg Pro Ile Gln Tyr Leu Cys Trp Ser Pro Val Gly Ser Lys Leu Ala 
            100                 105                 110         


Tyr Val Tyr Gln Asn Asn Ile Tyr Leu Lys Gln Arg Pro Glu Asp Pro 
        115                 120                 125             


Pro Phe Gln Ile Thr Tyr Asn Gly Lys Glu Asn Lys Ile Phe Asn Gly 
    130                 135                 140                 


Ile Pro Asp Trp Val Tyr Glu Glu Glu Met Leu Ala Thr Lys Tyr Ala 
145                 150                 155                 160 


Leu Trp Trp Ser Pro Asn Gly Arg Phe Leu Ala Tyr Ala Glu Phe Asn 
                165                 170                 175     


Asp Thr Glu Ile Pro Val Ile Ala Tyr Ser Tyr Tyr Gly Asp Glu Gln 
            180                 185                 190         


Tyr Pro Arg Thr Ile Asn Ile Pro Tyr Pro Lys Ala Gly Ala Lys Asn 
        195                 200                 205             


Pro Phe Val Arg Ile Phe Ile Ile Asp Thr Ser Tyr Pro Gly His Val 
    210                 215                 220                 


Gly Pro Arg Glu Val Pro Val Pro Ala Met Ile Ala Ser Ser Asp Tyr 
225                 230                 235                 240 


Tyr Phe Ser Trp Phe Thr Trp Val Thr Asp Asp Arg Ile Cys Leu Gln 
                245                 250                 255     


Trp Leu Lys Arg Ile Gln Asn Val Ser Val Leu Ser Ile Cys Asp Phe 
            260                 265                 270         


Arg Glu Asp Trp Gln Thr Trp Asn Cys Pro Lys Thr Gln Glu His Ile 
        275                 280                 285             


Glu Glu Ser Arg Thr Gly Trp Ala Gly Gly Phe Phe Val Ser Thr Pro 
    290                 295                 300                 


Val Phe Ser Tyr Asp Ala Ile Ser Tyr Tyr Lys Ile Phe Ser Asp Lys 
305                 310                 315                 320 


Asp Gly Tyr Lys His Ile His Tyr Ile Lys Asp Ser Val Glu Asn Ala 
                325                 330                 335     


Ile Gln Ile Thr Ser Gly Lys Trp Glu Ala Ile Asn Ile Phe Arg Val 
            340                 345                 350         


Thr Gln Asp Ser Leu Phe Tyr Ser Ser Asn Glu Phe Glu Gly Tyr Pro 
        355                 360                 365             


Gly Arg Arg Asn Ile Tyr Arg Ile Ser Ile Gly Ser His Pro Pro Ser 
    370                 375                 380                 


Lys Lys Cys Val Thr Cys His Leu Arg Glu Lys Arg Cys Gln Tyr Tyr 
385                 390                 395                 400 


Thr Ala Ser Phe Ser Asp Tyr Ala Lys Tyr Tyr Ala Leu Val Cys Tyr 
                405                 410                 415     


Gly Pro Gly Leu Pro Ile Ser Thr Leu His Asp Gly Arg Thr Asp Gln 
            420                 425                 430         


Glu Ile Lys Ile Leu Glu Glu Asn Lys Asp Leu Glu Tyr Ala Leu Lys 
        435                 440                 445             


Asn Ile Arg Leu Pro Lys Glu Glu Ile Lys Lys Leu Asp Val Asp Asp 
    450                 455                 460                 


Ile Thr Leu Trp Tyr Lys Met Ile Leu Pro Pro Gln Phe Asp Arg Ser 
465                 470                 475                 480 


Lys Lys Tyr Pro Leu Leu Ile Gln Val Tyr Gly Gly Pro Cys Ser Gln 
                485                 490                 495     


Ser Val Arg Ser Val Phe Ser Ile Arg Trp Ile Ser Tyr Leu Ala Ser 
            500                 505                 510         


Lys Glu Gly Ile Val Ile Ala Leu Val Asp Gly Arg Gly Thr Ala Phe 
        515                 520                 525             


Gln Gly Asp Lys Leu Leu Tyr Ala Val Tyr Arg Lys Leu Gly Val Tyr 
    530                 535                 540                 


Glu Val Glu Asp Gln Ile Thr Ala Val Arg Lys Phe Ile Glu Met Gly 
545                 550                 555                 560 


Phe Ile Asp Glu Lys Arg Ile Ala Ile Trp Gly Trp Ser Tyr Gly Gly 
                565                 570                 575     


Tyr Val Ser Ser Leu Ala Leu Ala Ser Gly Thr Gly Leu Phe Lys Cys 
            580                 585                 590         


Gly Ile Ala Val Ala Pro Val Ser Ser Trp Glu Tyr Tyr Ala Ser Ile 
        595                 600                 605             


Tyr Thr Glu Arg Phe Met Gly Leu Pro Thr Lys Asp Asp Asn Leu Glu 
    610                 615                 620                 


His Tyr Lys Asn Ser Thr Val Met Ala Arg Ala Glu Tyr Phe Arg Asn 
625                 630                 635                 640 


Val Asp Tyr Leu Leu Ile His Gly Thr Ala Asp Asp Asn Val His Phe 
                645                 650                 655     


Gln Asn Ser Ala Gln Ile Ala Lys Ala Leu Val Asn Ala Gln Val Asp 
            660                 665                 670         


Phe Gln Ala Met Trp Tyr Ser Asp Gln Asn His Gly Ile Ser Gly Leu 
        675                 680                 685             


Ser Thr Lys His Leu Tyr Thr His Met Thr His Phe Leu Lys Gln Cys 
    690                 695                 700                 


Phe Ser Leu Pro Asp 
705                 


<210>  74
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2 heavy chain in IgG4 format

<400>  74

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


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


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


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


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


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


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


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


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


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


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


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


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440             


<210>  75
<211>  1009
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mIL12-7NP2 conjugate

<400>  75

Met Trp Glu Leu Glu Lys Asp Val Tyr Val Val Glu Val Asp Trp Thr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Thr Val Asn Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln Arg His Gly Val Ile Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Thr Val Lys Glu Phe Leu Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Thr Leu Ser His Ser His Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asn Gly Ile Trp Ser Thr Glu Ile Leu Lys 
                85                  90                  95      


Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys Glu Ala Pro Asn Tyr Ser 
            100                 105                 110         


Gly Arg Phe Thr Cys Ser Trp Leu Val Gln Arg Asn Met Asp Leu Lys 
        115                 120                 125             


Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro Asp Ser Arg Ala Val Thr 
    130                 135                 140                 


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


Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln Glu Asp Val Thr Cys Pro 
                165                 170                 175     


Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu Ala Leu Glu Ala Arg Gln 
            180                 185                 190         


Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser Phe Phe Ile Arg Asp Ile 
        195                 200                 205             


Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Met Arg Pro Leu Lys Asn 
    210                 215                 220                 


Ser Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Ser Trp Ser Thr Pro 
225                 230                 235                 240 


His Ser Tyr Phe Ser Leu Lys Phe Phe Val Arg Ile Gln Arg Lys Lys 
                245                 250                 255     


Glu Lys Met Lys Glu Thr Glu Glu Gly Cys Asn Gln Lys Gly Ala Phe 
            260                 265                 270         


Leu Val Glu Arg Thr Ser Thr Glu Val Gln Cys Lys Gly Gly Asn Val 
        275                 280                 285             


Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn Ser Ser Cys Ser Lys Trp 
    290                 295                 300                 


Ala Cys Val Pro Cys Arg Val Arg Ser Gly Gly Gly Gly Ser Gly Gly 
305                 310                 315                 320 


Gly Gly Ser Gly Gly Gly Gly Ser Arg Val Ile Pro Val Ser Gly Pro 
                325                 330                 335     


Ala Arg Cys Leu Ser Gln Ser Arg Asn Leu Leu Lys Thr Thr Asp Asp 
            340                 345                 350         


Met Val Lys Thr Ala Arg Glu Lys Leu Lys His Tyr Ser Cys Thr Ala 
        355                 360                 365             


Glu Asp Ile Asp His Glu Asp Ile Thr Arg Asp Gln Thr Ser Thr Leu 
    370                 375                 380                 


Lys Thr Cys Leu Pro Leu Glu Leu His Lys Asn Glu Ser Cys Leu Ala 
385                 390                 395                 400 


Thr Arg Glu Thr Ser Ser Thr Thr Arg Gly Ser Cys Leu Pro Pro Gln 
                405                 410                 415     


Lys Thr Ser Leu Met Met Thr Leu Cys Leu Gly Ser Ile Tyr Glu Asp 
            420                 425                 430         


Leu Lys Met Tyr Gln Thr Glu Phe Gln Ala Ile Asn Ala Ala Leu Gln 
        435                 440                 445             


Asn His Asn His Gln Gln Ile Ile Leu Asp Lys Gly Met Leu Val Ala 
    450                 455                 460                 


Ile Asp Glu Leu Met Gln Ser Leu Asn His Asn Gly Glu Thr Leu Arg 
465                 470                 475                 480 


Gln Lys Pro Pro Val Gly Glu Ala Asp Pro Tyr Arg Val Lys Met Lys 
                485                 490                 495     


Leu Cys Ile Leu Leu His Ala Phe Ser Thr Arg Val Val Thr Ile Asn 
            500                 505                 510         


Arg Val Met Gly Tyr Leu Ser Ser Ala Gly Gly Gly Gly Ser Gly Gly 
        515                 520                 525             


Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu Ser Gly 
    530                 535                 540                 


Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
545                 550                 555                 560 


Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala 
                565                 570                 575     


Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly Gly 
            580                 585                 590         


Pro Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
        595                 600                 605             


Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala 
    610                 615                 620                 


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe Asp 
625                 630                 635                 640 


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser Gly 
                645                 650                 655     


Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro 
            660                 665                 670         


Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser 
        675                 680                 685             


Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu 
    690                 695                 700                 


Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe 
705                 710                 715                 720 


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu 
                725                 730                 735     


Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly 
            740                 745                 750         


Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Asp Ile Gly 
        755                 760                 765             


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Glu Val Gln Leu 
    770                 775                 780                 


Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 
785                 790                 795                 800 


Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp 
                805                 810                 815     


Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Gly 
            820                 825                 830         


Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
        835                 840                 845             


Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn 
    850                 855                 860                 


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Arg Leu 
865                 870                 875                 880 


Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                885                 890                 895     


Gly Gly Ser Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 
            900                 905                 910         


Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 
        915                 920                 925             


Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
    930                 935                 940                 


Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile 
945                 950                 955                 960 


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
                965                 970                 975     


Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
            980                 985                 990         


Ser Gly Lys Gly Pro Leu Thr Phe  Gly Gln Gly Thr Lys  Val Glu Ile 
        995                 1000                 1005             


Lys 
    


<210>  76
<211>  377
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2(Db)-huIL2 conjugate

<400>  76

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val Leu Thr Gln Ser 
        115                 120                 125             


Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 
    130                 135                 140                 


Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 
145                 150                 155                 160 


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 
                165                 170                 175     


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            180                 185                 190         


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 
        195                 200                 205             


Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr 
    210                 215                 220                 


Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
225                 230                 235                 240 


Gly Gly Gly Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu 
                245                 250                 255     


Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile 
            260                 265                 270         


Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe 
        275                 280                 285             


Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu 
    290                 295                 300                 


Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys 
305                 310                 315                 320 


Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile 
                325                 330                 335     


Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala 
            340                 345                 350         


Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe 
        355                 360                 365             


Cys Gln Ser Ile Ile Ser Thr Leu Thr 
    370                 375         


<210>  77
<211>  65
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Sushi Domain of the IL15 Receptor alpha

<400>  77

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg 
65  


<210>  78
<211>  114
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human Interleukin 15 (huIL15)

<400>  78

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  79
<211>  687
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  7NP2(scDb)-SD-huIL15 conjugate

<400>  79

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val Leu Thr Gln Ser 
        115                 120                 125             


Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 
    130                 135                 140                 


Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 
145                 150                 155                 160 


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 
                165                 170                 175     


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            180                 185                 190         


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 
        195                 200                 205             


Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr 
    210                 215                 220                 


Lys Val Glu Ile Lys Asp Ile Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


Gly Gly Gly Gly Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val 
                245                 250                 255     


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 
            260                 265                 270         


Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
        275                 280                 285             


Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr Tyr 
    290                 295                 300                 


Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
305                 310                 315                 320 


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
                325                 330                 335     


Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly Gln 
            340                 345                 350         


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Glu Ile Val 
        355                 360                 365             


Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 
    370                 375                 380                 


Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 
385                 390                 395                 400 


Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 
                405                 410                 415     


Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 
            420                 425                 430         


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


Phe Ala Val Tyr Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe 
    450                 455                 460                 


Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Ile Thr Cys Pro Pro Pro Met Ser 
                485                 490                 495     


Val Glu His Ala Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg 
            500                 505                 510         


Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser 
        515                 520                 525             


Ser Leu Thr Glu Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp 
    530                 535                 540                 


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


Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Leu Gln Asn Trp Val 
                565                 570                 575     


Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met 
            580                 585                 590         


His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys 
        595                 600                 605             


Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser 
    610                 615                 620                 


Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile 
625                 630                 635                 640 


Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser 
                645                 650                 655     


Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe 
            660                 665                 670         


Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser 
        675                 680                 685         


<210>  80
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker between p40 and p35 in the single-chain IL12, between IL12
       and 7NP2 VH in IL12-7NP2 conjugate, between 7NP2 VL and IL2 in 
       7NP2(Db)-IL2 conjugate and between 7NP2 VL and SD in 
       7NP2(scDb)-SD-huIL15 conjugate

<400>  80

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  81
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker connecting the Sushi Domain (SD) to huIL15 in the 
       7NP2(scDb)-SD-huIL15 conjugate

<400>  81

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly 
1               5                   10                  15      


Gly Ser Leu Gln 
            20  


<210>  82
<211>  562
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL2-7NP2-TNF?mut v2 conjugate

<400>  82

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His 
1               5                   10                  15      


Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys 
            20                  25                  30          


Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys 
        35                  40                  45              


Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys 
    50                  55                  60                  


Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu 
65                  70                  75                  80  


Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu 
                85                  90                  95      


Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala 
            100                 105                 110         


Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile 
        115                 120                 125             


Ile Ser Thr Leu Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    130                 135                 140                 


Gly Gly Gly Ser Lys Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu 
145                 150                 155                 160 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                165                 170                 175     


Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
            180                 185                 190         


Gly Leu Glu Trp Val Ser Ala Ile Gly Ser Val Gly Gly Pro Thr Tyr 
        195                 200                 205             


Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    210                 215                 220                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
225                 230                 235                 240 


Ala Val Tyr Tyr Cys Ala Lys Arg Leu Ala Trp Phe Asp Tyr Trp Gly 
                245                 250                 255     


Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly 
            260                 265                 270         


Gly Gly Ser Gly Gly Gly Gly Ser Lys Glu Ile Val Leu Thr Gln Ser 
        275                 280                 285             


Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 
    290                 295                 300                 


Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln 
305                 310                 315                 320 


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 
                325                 330                 335     


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            340                 345                 350         


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 
        355                 360                 365             


Tyr Cys Gln Gln Ser Gly Lys Gly Pro Leu Thr Phe Gly Gln Gly Thr 
    370                 375                 380                 


Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
385                 390                 395                 400 


Gly Gly Gly Ser Lys Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys 
                405                 410                 415     


Pro Val Ala His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln 
            420                 425                 430         


Trp Leu Asn Arg Ala Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu 
        435                 440                 445             


Arg Asp Asn Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr 
    450                 455                 460                 


Ser Gln Val Leu Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu 
465                 470                 475                 480 


Leu Thr His Thr Ile Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val 
                485                 490                 495     


Asn Leu Leu Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu 
            500                 505                 510         


Gly Ala Glu Ala Lys Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val 
        515                 520                 525             


Phe Gln Leu Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro 
    530                 535                 540                 


Asp Tyr Leu Asp Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile 
545                 550                 555                 560 


Ala Leu 
        


<210>  83
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker between IL2 and 7NP2, between VH and VL in 7NP2, and 
       between 7NP2 and TNF?mut in the IL2-7NP2-TNF?mut v2 conjugate

<400>  83

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Lys 
1               5                   10                  15      


<210>  84
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAT2 primer

<400>  84
gcttgacact gtgaccagtg tcccttgacc ccaatagtcg aaccaagcca                  50


<210>  85
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAT3 primer

<400>  85
tggcttggtt cgactattgg ggtcaaggga cactggtcac agtgtcaagc                  50


