                         SEQUENCE LISTING

<110>  PHILOGEN S.P.A.
 
<120>  IL2 and TNF Immunoconjugates

<130>  TEK/FP7195233

<150>  GB1507908.0
<151>  2015-05-08

<160>  47    

<170>  PatentIn version 3.3

<210>  1
<211>  557
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the huIL2-F8-huTNF alpha 
       [soluble form] conjugate

<400>  1

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 Leu 
                165                 170                 175     


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


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


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


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


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


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


Met Arg Gly Arg Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
    370                 375                 380                 


Lys Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
385                 390                 395                 400 


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


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


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


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


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


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


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


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


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


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


<210>  2
<211>  118
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8 VH domain

<400>  2

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 Leu Phe 
            20                  25                  30          


Thr 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 Thr His Leu Tyr Leu Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  3
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the linker linking the F8 VH 
       domain to the F8 VL domain

<400>  3

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


<210>  4
<211>  108
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8 VL domain

<400>  4

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 Met Pro 
            20                  25                  30          


Phe 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 Met Arg Gly Arg Pro 
                85                  90                  95      


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


<210>  5
<211>  240
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8 scFv

<400>  5

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 Leu Phe 
            20                  25                  30          


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


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


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


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


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


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met 
    210                 215                 220                 


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


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

<220>
<223>  Synthetic F8 CDR1 VH

<400>  6

Leu Phe Thr 
1           


<210>  7
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F8 CDR2 VH

<400>  7

Ser Gly Ser Gly Gly Ser 
1               5       


<210>  8
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F8 CDR3 VH

<400>  8

Ser Thr His Leu Tyr Leu 
1               5       


<210>  9
<211>  3
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F8 CDR1 VL

<400>  9

Met Pro Phe 
1           


<210>  10
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F8 CDR2 VL

<400>  10

Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210>  11
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F8 CDR3 VL

<400>  11

Met Arg Gly Arg Pro Pro 
1               5       


<210>  12
<211>  133
<212>  PRT
<213>  Homo sapiens

<400>  12

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>  13
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the linker linking: huIL2 to the
       F8 VH domain in the huIL2-F8-huTNF alpha conjugates, huTNF alpha 
       to the F8 VH domain in the huTNF alpha-F8-huIL2 conjugates, and 
       huTNF alpha to huIL2 in the F8-huIL2-huTNF alpha conjugates

<400>  13

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


<210>  14
<211>  15
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the linker linking: huTNF alpha 
       to the F8 VL domain in the huIL2-F8-huTNF alpha conjugates, huIL2
       to the F8 VL domain in the huTNF alpha-F8-huIL2 conjugates, and 
       huIL2 to the F8 VL domain in the F8-huIL2-huTNF alpha conjugates

<400>  14

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


<210>  15
<211>  157
<212>  PRT
<213>  Homo sapiens

<400>  15

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 Arg 
            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>  16
<211>  572
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the muIL2-F8-muTNF alpha 
       conjugate

<400>  16

Ala Pro Thr Ser Ser Ser Thr Ser Ser Ser Thr Ala Glu Ala Gln Gln 
1               5                   10                  15      


Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln His Leu Glu Gln Leu Leu 
            20                  25                  30          


Met Asp Leu Gln Glu Leu Leu Ser Arg Met Glu Asn Tyr Arg Asn Leu 
        35                  40                  45              


Lys Leu Pro Arg Met Leu Thr Phe Lys Phe Tyr Leu Pro Lys Gln Ala 
    50                  55                  60                  


Thr Glu Leu Lys Asp Leu Gln Cys Leu Glu Asp Glu Leu Gly Pro Leu 
65                  70                  75                  80  


Arg His Val Leu Asp Leu Thr Gln Ser Lys Ser Phe Gln Leu Glu Asp 
                85                  90                  95      


Ala Glu Asn Phe Ile Ser Asn Ile Arg Val Thr Val Val Lys Leu Lys 
            100                 105                 110         


Gly Ser Asp Asn Thr Phe Glu Cys Gln Phe Asp Asp Glu Ser Ala Thr 
        115                 120                 125             


Val Val Asp Phe Leu Arg Arg Trp Ile Ala Phe Cys Gln Ser Ile Ile 
    130                 135                 140                 


Ser Thr Ser Pro Gln Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala 
145                 150                 155                 160 


Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
                165                 170                 175     


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Leu 
            180                 185                 190         


Phe Thr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
        195                 200                 205             


Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser 
    210                 215                 220                 


Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 
225                 230                 235                 240 


Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 
                245                 250                 255     


Cys Ala Lys Ser Thr His Leu Tyr Leu Phe Asp Tyr Trp Gly Gln Gly 
            260                 265                 270         


Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        275                 280                 285             


Ser Gly Gly Gly Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 
    290                 295                 300                 


Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln 
305                 310                 315                 320 


Ser Val Ser Met Pro Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                325                 330                 335     


Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile 
            340                 345                 350         


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
        355                 360                 365             


Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln 
    370                 375                 380                 


Met Arg Gly Arg Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
385                 390                 395                 400 


Lys Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
                405                 410                 415     


Leu Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val 
            420                 425                 430         


Val Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg 
        435                 440                 445             


Ala Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu 
    450                 455                 460                 


Val Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe 
465                 470                 475                 480 


Lys Gly Gln Gly Cys Pro Asp Tyr Val Leu Leu Thr His Thr Val Ser 
                485                 490                 495     


Arg Phe Ala Ile Ser Tyr Gln Glu Lys Val Asn Leu Leu Ser Ala Val 
            500                 505                 510         


Lys Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro 
        515                 520                 525             


Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly 
    530                 535                 540                 


Asp Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala 
545                 550                 555                 560 


Glu Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu 
                565                 570         


<210>  17
<211>  149
<212>  PRT
<213>  Mus musculus

<400>  17

Ala Pro Thr Ser Ser Ser Thr Ser Ser Ser Thr Ala Glu Ala Gln Gln 
1               5                   10                  15      


Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln His Leu Glu Gln Leu Leu 
            20                  25                  30          


Met Asp Leu Gln Glu Leu Leu Ser Arg Met Glu Asn Tyr Arg Asn Leu 
        35                  40                  45              


Lys Leu Pro Arg Met Leu Thr Phe Lys Phe Tyr Leu Pro Lys Gln Ala 
    50                  55                  60                  


Thr Glu Leu Lys Asp Leu Gln Cys Leu Glu Asp Glu Leu Gly Pro Leu 
65                  70                  75                  80  


Arg His Val Leu Asp Leu Thr Gln Ser Lys Ser Phe Gln Leu Glu Asp 
                85                  90                  95      


Ala Glu Asn Phe Ile Ser Asn Ile Arg Val Thr Val Val Lys Leu Lys 
            100                 105                 110         


Gly Ser Asp Asn Thr Phe Glu Cys Gln Phe Asp Asp Glu Ser Ala Thr 
        115                 120                 125             


Val Val Asp Phe Leu Arg Arg Trp Ile Ala Phe Cys Gln Ser Ile Ile 
    130                 135                 140                 


Ser Thr Ser Pro Gln 
145                 


<210>  18
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the linker linking muIL2 to F8 
       VH domain in the muIL2-F8-muTNF alpha conjugate

<400>  18

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


<210>  19
<211>  15
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the linker linking muTNF alpha 
       to the F8 VL domain in the muIL2-F8-muTNF alpha conjugate

<400>  19

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


<210>  20
<211>  156
<212>  PRT
<213>  Mus musculus

<400>  20

Leu Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val 
1               5                   10                  15      


Val Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg 
            20                  25                  30          


Ala Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu 
        35                  40                  45              


Val Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe 
    50                  55                  60                  


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


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


Lys Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro 
            100                 105                 110         


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


Asp Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala 
    130                 135                 140                 


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


<210>  21
<211>  5
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR1 VH

<400>  21

Ser Phe Ser Met Ser 
1               5   


<210>  22
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR2 VH

<400>  22

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


<210>  23
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR3 VH

<400>  23

Pro Phe Pro Tyr Phe Asp Tyr 
1               5           


<210>  24
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR1 VL

<400>  24

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


<210>  25
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR2 VL

<400>  25

Tyr Ala Ser Ser Arg Ala Thr 
1               5           


<210>  26
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic L19 CDR3 VL

<400>  26

Gln Gln Thr Gly Arg Ile Pro Pro Thr 
1               5                   


<210>  27
<211>  116
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of L19 VH domain

<400>  27

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 Phe 
            20                  25                  30          


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


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


Thr Val Ser Ser 
        115     


<210>  28
<211>  108
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of L19 VL domain

<400>  28

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          


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


Ile Tyr Tyr 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 Thr Gly Arg Ile Pro 
                85                  90                  95      


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


<210>  29
<211>  236
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of scFv(L19)

<400>  29

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 Phe 
            20                  25                  30          


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


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


Thr Val Ser Ser Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala Ser 
        115                 120                 125             


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


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


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


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


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Thr Gly Arg Ile Pro 
    210                 215                 220                 


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


<210>  30
<211>  5
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR1 VH

<400>  30

Arg Tyr Gly Met Ser 
1               5   


<210>  31
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR2 VH

<400>  31

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


Gly 
    


<210>  32
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR3 VH

<400>  32

Ala His Asn Ala Phe Asp Tyr 
1               5           


<210>  33
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR1 VL

<400>  33

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser 
1               5                   10      


<210>  34
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR2 VL

<400>  34

Gly Lys Asn Asn Arg Pro Ser 
1               5           


<210>  35
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic F16 CDR3 VL

<400>  35

Asn Ser Ser Val Tyr Thr Met Pro Pro Val Val 
1               5                   10      


<210>  36
<211>  116
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence F16 VH domain

<400>  36

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 Arg Tyr 
            20                  25                  30          


Gly 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 Ala His Asn Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Arg 
        115     


<210>  37
<211>  109
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence F16 VL domain

<400>  37

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 Asn Ser Ser Val Tyr Thr Met Pro Pro 
                85                  90                  95      


Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 


<210>  38
<211>  235
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the scFv(F16)

<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 Arg Tyr 
            20                  25                  30          


Gly 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 Ala His Asn Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


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


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


Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys 
                165                 170                 175     


Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser 
            180                 185                 190         


Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu 
        195                 200                 205             


Ala Asp Tyr Tyr Cys Asn Ser Ser Val Tyr Thr Met Pro Pro Val Val 
    210                 215                 220                 


Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
225                 230                 235 


<210>  39
<211>  577
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the huIL2-F8-huTNF alpha   
       [extracellular domain] conjugate

<400>  39

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 Leu 
                165                 170                 175     


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


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


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


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


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


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


Met Arg Gly Arg Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
    370                 375                 380                 


Lys Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
385                 390                 395                 400 


Gly Pro Gln Arg Glu Glu Phe Pro Arg Asp Leu Ser Leu Ile Ser Pro 
                405                 410                 415     


Leu Ala Gln Ala Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro 
            420                 425                 430         


Val Ala His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp 
        435                 440                 445             


Leu Asn Arg Arg Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg 
    450                 455                 460                 


Asp Asn Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser 
465                 470                 475                 480 


Gln Val Leu Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu 
                485                 490                 495     


Thr His Thr Ile Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn 
            500                 505                 510         


Leu Leu Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly 
        515                 520                 525             


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


Gln Leu Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp 
545                 550                 555                 560 


Tyr Leu Asp Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala 
                565                 570                 575     


Leu 
    


<210>  40
<211>  177
<212>  PRT
<213>  Homo sapiens

<400>  40

Gly Pro Gln Arg Glu Glu Phe Pro Arg Asp Leu Ser Leu Ile Ser Pro 
1               5                   10                  15      


Leu Ala Gln Ala Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro 
            20                  25                  30          


Val Ala His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp 
        35                  40                  45              


Leu Asn Arg Arg Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg 
    50                  55                  60                  


Asp Asn Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser 
65                  70                  75                  80  


Gln Val Leu Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu 
                85                  90                  95      


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


Leu Leu Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly 
        115                 120                 125             


Ala Glu Ala Lys Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe 
    130                 135                 140                 


Gln Leu Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp 
145                 150                 155                 160 


Tyr Leu Asp Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala 
                165                 170                 175     


Leu 
    


<210>  41
<211>  557
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the huTNF alpha [soluble 
       form]-F8-huIL2 conjugate

<400>  41

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 Arg 
            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 Gly Asp Gly 
145                 150                 155                 160 


Ser Ser Gly Gly Ser Gly Gly Ala Ser Glu Val Gln Leu Leu Glu Ser 
                165                 170                 175     


Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala 
            180                 185                 190         


Ala Ser Gly Phe Thr Phe Ser Leu Phe Thr Met Ser Trp Val Arg Gln 
        195                 200                 205             


Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly 
    210                 215                 220                 


Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser 
225                 230                 235                 240 


Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg 
                245                 250                 255     


Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Ser Thr His Leu Tyr 
            260                 265                 270         


Leu Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly 
        275                 280                 285             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Glu Ile Val 
    290                 295                 300                 


Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala 
305                 310                 315                 320 


Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Met Pro Phe Leu Ala 
                325                 330                 335     


Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly 
            340                 345                 350         


Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly 
        355                 360                 365             


Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp 
    370                 375                 380                 


Phe Ala Val Tyr Tyr Cys Gln Gln Met Arg Gly Arg Pro Pro Thr Phe 
385                 390                 395                 400 


Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ser Ser Gly Ser Ser 
                405                 410                 415     


Ser Ser Gly Ser Ser Ser Ser Gly Ala Pro Thr Ser Ser Ser Thr Lys 
            420                 425                 430         


Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile 
        435                 440                 445             


Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu 
    450                 455                 460                 


Thr Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu 
465                 470                 475                 480 


Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu 
                485                 490                 495     


Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn 
            500                 505                 510         


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


Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg 
    530                 535                 540                 


Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr 
545                 550                 555         


<210>  42
<211>  577
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the huTNF alpha [extracellular 
       domain]-F8-huIL2 conjugate

<400>  42

Gly Pro Gln Arg Glu Glu Phe Pro Arg Asp Leu Ser Leu Ile Ser Pro 
1               5                   10                  15      


Leu Ala Gln Ala Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro 
            20                  25                  30          


Val Ala His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp 
        35                  40                  45              


Leu Asn Arg Arg Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg 
    50                  55                  60                  


Asp Asn Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser 
65                  70                  75                  80  


Gln Val Leu Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu 
                85                  90                  95      


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


Leu Leu Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly 
        115                 120                 125             


Ala Glu Ala Lys Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe 
    130                 135                 140                 


Gln Leu Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp 
145                 150                 155                 160 


Tyr Leu Asp Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala 
                165                 170                 175     


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


Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
        195                 200                 205             


Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Leu Phe Thr Met Ser 
    210                 215                 220                 


Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile 
225                 230                 235                 240 


Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
                245                 250                 255     


Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met 
            260                 265                 270         


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Ser 
        275                 280                 285             


Thr His Leu Tyr Leu Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr 
    290                 295                 300                 


Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
305                 310                 315                 320 


Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro 
                325                 330                 335     


Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Met 
            340                 345                 350         


Pro Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu 
        355                 360                 365             


Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe 
    370                 375                 380                 


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu 
385                 390                 395                 400 


Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met Arg Gly Arg 
                405                 410                 415     


Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ser 
            420                 425                 430         


Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ala Pro Thr Ser 
        435                 440                 445             


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


Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu 
465                 470                 475                 480 


Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu 
                485                 490                 495     


Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu 
            500                 505                 510         


Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp 
        515                 520                 525             


Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu 
    530                 535                 540                 


Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu 
545                 550                 555                 560 


Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu 
                565                 570                 575     


Thr 
    


<210>  43
<211>  557
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8-huIL2-huTNF alpha 
       [soluble form] conjugate

<400>  43

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 Leu Phe 
            20                  25                  30          


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


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


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


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


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


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met 
    210                 215                 220                 


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


Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ala 
                245                 250                 255     


Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu 
            260                 265                 270         


Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn 
        275                 280                 285             


Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys 
    290                 295                 300                 


Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro 
305                 310                 315                 320 


Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg 
                325                 330                 335     


Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys 
            340                 345                 350         


Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr 
        355                 360                 365             


Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile 
    370                 375                 380                 


Ser Thr Leu Thr Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala Ser 
385                 390                 395                 400 


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


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


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


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


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


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


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


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


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


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


<210>  44
<211>  577
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8-huIL2- huTNF alpha   
       [extracellular domain] conjugate

<400>  44

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 Leu Phe 
            20                  25                  30          


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


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


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


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


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


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met 
    210                 215                 220                 


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


Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ala 
                245                 250                 255     


Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His Leu 
            260                 265                 270         


Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn 
        275                 280                 285             


Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys 
    290                 295                 300                 


Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro 
305                 310                 315                 320 


Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu Arg 
                325                 330                 335     


Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu Lys 
            340                 345                 350         


Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr 
        355                 360                 365             


Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Cys Gln Ser Ile Ile 
    370                 375                 380                 


Ser Thr Leu Thr Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala Ser 
385                 390                 395                 400 


Gly Pro Gln Arg Glu Glu Phe Pro Arg Asp Leu Ser Leu Ile Ser Pro 
                405                 410                 415     


Leu Ala Gln Ala Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro 
            420                 425                 430         


Val Ala His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp 
        435                 440                 445             


Leu Asn Arg Arg Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg 
    450                 455                 460                 


Asp Asn Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser 
465                 470                 475                 480 


Gln Val Leu Phe Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu 
                485                 490                 495     


Thr His Thr Ile Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn 
            500                 505                 510         


Leu Leu Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly 
        515                 520                 525             


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


Gln Leu Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp 
545                 550                 555                 560 


Tyr Leu Asp Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala 
                565                 570                 575     


Leu 
    


<210>  45
<211>  572
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the muTNF alpha -F8-muIL2 
       conjugate

<400>  45

Leu Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val 
1               5                   10                  15      


Val Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg 
            20                  25                  30          


Ala Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu 
        35                  40                  45              


Val Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe 
    50                  55                  60                  


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


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


Lys Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro 
            100                 105                 110         


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


Asp Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala 
    130                 135                 140                 


Glu Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu Gly Asp Gly Ser 
145                 150                 155                 160 


Ser Gly Gly Ser Gly Gly Ala Ser Glu Val Gln Leu Leu Glu Ser Gly 
                165                 170                 175     


Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
            180                 185                 190         


Ser Gly Phe Thr Phe Ser Leu Phe Thr Met Ser Trp Val Arg Gln Ala 
        195                 200                 205             


Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly 
    210                 215                 220                 


Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
225                 230                 235                 240 


Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala 
                245                 250                 255     


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Ser Thr His Leu Tyr Leu 
            260                 265                 270         


Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly 
        275                 280                 285             


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Glu Ile Val Leu 
    290                 295                 300                 


Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr 
305                 310                 315                 320 


Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Met Pro Phe Leu Ala Trp 
                325                 330                 335     


Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala 
            340                 345                 350         


Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser 
        355                 360                 365             


Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe 
    370                 375                 380                 


Ala Val Tyr Tyr Cys Gln Gln Met Arg Gly Arg Pro Pro Thr Phe Gly 
385                 390                 395                 400 


Gln Gly Thr Lys Val Glu Ile Lys Ser Ser Ser Ser Gly Ser Ser Ser 
                405                 410                 415     


Ser Gly Ser Ser Ser Ser Gly Ala Pro Thr Ser Ser Ser Thr Ser Ser 
            420                 425                 430         


Ser Thr Ala Glu Ala Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 
        435                 440                 445             


Gln His Leu Glu Gln Leu Leu Met Asp Leu Gln Glu Leu Leu Ser Arg 
    450                 455                 460                 


Met Glu Asn Tyr Arg Asn Leu Lys Leu Pro Arg Met Leu Thr Phe Lys 
465                 470                 475                 480 


Phe Tyr Leu Pro Lys Gln Ala Thr Glu Leu Lys Asp Leu Gln Cys Leu 
                485                 490                 495     


Glu Asp Glu Leu Gly Pro Leu Arg His Val Leu Asp Leu Thr Gln Ser 
            500                 505                 510         


Lys Ser Phe Gln Leu Glu Asp Ala Glu Asn Phe Ile Ser Asn Ile Arg 
        515                 520                 525             


Val Thr Val Val Lys Leu Lys Gly Ser Asp Asn Thr Phe Glu Cys Gln 
    530                 535                 540                 


Phe Asp Asp Glu Ser Ala Thr Val Val Asp Phe Leu Arg Arg Trp Ile 
545                 550                 555                 560 


Ala Phe Cys Gln Ser Ile Ile Ser Thr Ser Pro Gln 
                565                 570         


<210>  46
<211>  572
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of the F8-muIL2-muTNF alpha  
       conjugate

<400>  46

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 Leu Phe 
            20                  25                  30          


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


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


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


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


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


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met 
    210                 215                 220                 


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


Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ala 
                245                 250                 255     


Pro Thr Ser Ser Ser Thr Ser Ser Ser Thr Ala Glu Ala Gln Gln Gln 
            260                 265                 270         


Gln Gln Gln Gln Gln Gln Gln Gln Gln His Leu Glu Gln Leu Leu Met 
        275                 280                 285             


Asp Leu Gln Glu Leu Leu Ser Arg Met Glu Asn Tyr Arg Asn Leu Lys 
    290                 295                 300                 


Leu Pro Arg Met Leu Thr Phe Lys Phe Tyr Leu Pro Lys Gln Ala Thr 
305                 310                 315                 320 


Glu Leu Lys Asp Leu Gln Cys Leu Glu Asp Glu Leu Gly Pro Leu Arg 
                325                 330                 335     


His Val Leu Asp Leu Thr Gln Ser Lys Ser Phe Gln Leu Glu Asp Ala 
            340                 345                 350         


Glu Asn Phe Ile Ser Asn Ile Arg Val Thr Val Val Lys Leu Lys Gly 
        355                 360                 365             


Ser Asp Asn Thr Phe Glu Cys Gln Phe Asp Asp Glu Ser Ala Thr Val 
    370                 375                 380                 


Val Asp Phe Leu Arg Arg Trp Ile Ala Phe Cys Gln Ser Ile Ile Ser 
385                 390                 395                 400 


Thr Ser Pro Gln Gly Asp Gly Ser Ser Gly Gly Ser Gly Gly Ala Ser 
                405                 410                 415     


Leu Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val 
            420                 425                 430         


Val Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg 
        435                 440                 445             


Ala Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu 
    450                 455                 460                 


Val Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe 
465                 470                 475                 480 


Lys Gly Gln Gly Cys Pro Asp Tyr Val Leu Leu Thr His Thr Val Ser 
                485                 490                 495     


Arg Phe Ala Ile Ser Tyr Gln Glu Lys Val Asn Leu Leu Ser Ala Val 
            500                 505                 510         


Lys Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro 
        515                 520                 525             


Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly 
    530                 535                 540                 


Asp Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala 
545                 550                 555                 560 


Glu Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu 
                565                 570         


<210>  47
<211>  411
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Amino acid sequence of F8-muTNF alpha  conjugate

<400>  47

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 Leu Phe 
            20                  25                  30          


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


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


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


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


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


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Met 
    210                 215                 220                 


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


Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Leu 
                245                 250                 255     


Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val Val 
            260                 265                 270         


Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg Ala 
        275                 280                 285             


Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu Val 
    290                 295                 300                 


Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe Lys 
305                 310                 315                 320 


Gly Gln Gly Cys Pro Asp Tyr Val Leu Leu Thr His Thr Val Ser Arg 
                325                 330                 335     


Phe Ala Ile Ser Tyr Gln Glu Lys Val Asn Leu Leu Ser Ala Val Lys 
            340                 345                 350         


Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro Trp 
        355                 360                 365             


Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp 
    370                 375                 380                 


Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala Glu 
385                 390                 395                 400 


Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu 
                405                 410     


