                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Precursor proteins and kit for targeted therapy

<130>  P36624-WO

<150>  EP20215328.4
<151>  2020-12-18

<160>  45    

<170>  PatentIn version 3.5

<210>  1
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VH_CH1_Dig-VH_CH3-Knob]

<400>  1

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


Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Asp Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


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


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


Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Leu Ala Trp Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


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


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


Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu 
        275                 280                 285             


Trp Val Ser Ser Ile Asn Ile Gly Ala Thr Tyr Ile Tyr Tyr Ala Asp 
    290                 295                 300                 


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


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


Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys Ala Tyr Tyr 
            340                 345                 350         


Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly 
        355                 360                 365             


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
    370                 375                 380                 


Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
385                 390                 395                 400 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                405                 410                 415     


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
            420                 425                 430         


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
        435                 440                 445             


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
    450                 455                 460                 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470                 


<210>  2
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VL_Ckappa]

<400>  2

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ile Ile Val His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


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


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


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  3
<211>  359
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Dig-VL_CH3-Hole]-[Linker]-[Human interleukin-4]

<400>  3

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Lys Asn Tyr 
            20                  25                  30          


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


Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr Leu Pro Pro 
                85                  90                  95      


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


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


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Ser Thr Leu Cys Thr Glu 
                245                 250                 255     


Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Glu Lys 
            260                 265                 270         


Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His 
        275                 280                 285             


His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His 
    290                 295                 300                 


Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu 
305                 310                 315                 320 


Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln 
                325                 330                 335     


Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu 
            340                 345                 350         


Lys Tyr Ser Lys Cys Ser Ser 
        355                 


<210>  4
<211>  366
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Dig-VL_CH3-Hole]-[Linker]-[Interleukin-4 DABC (circularly 
       permutated)]

<400>  4

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Lys Asn Tyr 
            20                  25                  30          


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


Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr Leu Pro Pro 
                85                  90                  95      


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


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


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn 
225                 230                 235                 240 


Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys 
                245                 250                 255     


Ser Ser Gly Gly Gly Ser Gly Gly Ser His Lys Cys Asp Ile Thr Leu 
            260                 265                 270         


Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Ser Thr 
        275                 280                 285             


Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn 
    290                 295                 300                 


Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln 
305                 310                 315                 320 


Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala 
                325                 330                 335     


Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu 
            340                 345                 350         


Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro 
        355                 360                 365     


<210>  5
<211>  600
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[Split interleukin-4 
       (BCD)]

<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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


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


Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
            260                 265                 270         


Thr Phe Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys 
        275                 280                 285             


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


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


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


Ala Val Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys 
            340                 345                 350         


Ala Tyr Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val 
        355                 360                 365             


Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Leu Cys Thr 
                485                 490                 495     


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


Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser 
        515                 520                 525             


His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe 
    530                 535                 540                 


His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn 
545                 550                 555                 560 


Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn 
                565                 570                 575     


Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg 
            580                 585                 590         


Glu Lys Tyr Ser Lys Ser Ser Ser 
        595                 600 


<210>  6
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VL_Ckappa]

<400>  6

Glu Ile Val Leu Thr Gln Ser Pro Ala 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 Tyr 
            20                  25                  30          


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


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


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  7
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A) E9Q]

<400>  7

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ile Thr Leu Gln Gln Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  8
<211>  495
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[Split interleukin-4 (A)]

<400>  8

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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 
                245                 250                 255     


Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 
            260                 265                 270         


Asp Ile Lys Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 
        275                 280                 285             


Pro Lys Leu Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro 
    290                 295                 300                 


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
305                 310                 315                 320 


Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser 
                325                 330                 335     


Ile Thr Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            340                 345                 350         


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
        355                 360                 365             


Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 
    370                 375                 380                 


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
385                 390                 395                 400 


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


Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
            420                 425                 430         


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
        435                 440                 445             


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Lys Ser Asp Ile Thr 
465                 470                 475                 480 


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


<210>  9
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       R88Q]

<400>  9

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  10
<211>  598
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Her2-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[Split interleukin-4 
       (BCD)]

<400>  10

Glu Val Gln Leu Val 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 Asn Ile Lys Asp Thr 
            20                  25                  30          


Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


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


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


Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 
        275                 280                 285             


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


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


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


Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys Ala Tyr 
            340                 345                 350         


Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        355                 360                 365             


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
    370                 375                 380                 


Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 
385                 390                 395                 400 


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
                405                 410                 415     


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
            420                 425                 430         


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
        435                 440                 445             


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
    450                 455                 460                 


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser 
465                 470                 475                 480 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Leu Cys Thr Glu Leu 
                485                 490                 495     


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


Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His 
        515                 520                 525             


Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg 
    530                 535                 540                 


His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp 
545                 550                 555                 560 


Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser 
                565                 570                 575     


Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys 
            580                 585                 590         


Tyr Ser Lys Ser Ser Ser 
        595             


<210>  11
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Her2-VL_Ckappa]

<400>  11

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 
            20                  25                  30          


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


Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  12
<211>  493
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Her2-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[Split interleukin-4 (A)]

<400>  12

Glu Val Gln Leu Val 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 Asn Ile Lys Asp Thr 
            20                  25                  30          


Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
                245                 250                 255     


Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile 
            260                 265                 270         


Lys Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
        275                 280                 285             


Leu Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg 
    290                 295                 300                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
305                 310                 315                 320 


Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr 
                325                 330                 335     


Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gln 
            340                 345                 350         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
        355                 360                 365             


Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
    370                 375                 380                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
385                 390                 395                 400 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                405                 410                 415     


Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            420                 425                 430         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        435                 440                 445             


Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly 
    450                 455                 460                 


Gly Gly Ser Gly Gly Gly Gly Ser His Lys Ser Asp Ile Thr Leu Gln 
465                 470                 475                 480 


Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                485                 490             


<210>  13
<211>  477
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VH_CH3-Knob]

<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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


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


Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
            260                 265                 270         


Thr Phe Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys 
        275                 280                 285             


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


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


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


Ala Val Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys 
            340                 345                 350         


Ala Tyr Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val 
        355                 360                 365             


Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470                 475         


<210>  14
<211>  571
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[Split interleukin-4 (BC)]

<400>  14

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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


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


Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
            260                 265                 270         


Thr Phe Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys 
        275                 280                 285             


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


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


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


Ala Val Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys 
            340                 345                 350         


Ala Tyr Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val 
        355                 360                 365             


Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Leu Cys Thr 
                485                 490                 495     


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


Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser 
        515                 520                 525             


His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe 
    530                 535                 540                 


His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn 
545                 550                 555                 560 


Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro 
                565                 570     


<210>  15
<211>  286
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (DA) 
       E9Q]

<400>  15

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn 
225                 230                 235                 240 


Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys 
                245                 250                 255     


Ser Ser Gly Gly Gly Ser Gly Gly Ser His Lys Cys Asp Ile Thr Leu 
            260                 265                 270         


Gln Gln Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
        275                 280                 285     


<210>  16
<211>  531
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[Split interleukin-4 (DA)]

<400>  16

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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 
                245                 250                 255     


Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 
            260                 265                 270         


Asp Ile Lys Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 
        275                 280                 285             


Pro Lys Leu Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro 
    290                 295                 300                 


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
305                 310                 315                 320 


Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser 
                325                 330                 335     


Ile Thr Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            340                 345                 350         


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
        355                 360                 365             


Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 
    370                 375                 380                 


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
385                 390                 395                 400 


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


Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
            420                 425                 430         


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
        435                 440                 445             


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Lys Glu Ala Asn Gln 
465                 470                 475                 480 


Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu 
                485                 490                 495     


Lys Tyr Ser Lys Cys Ser Ser Gly Gly Gly Ser Gly Gly Ser His Lys 
            500                 505                 510         


Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr 
        515                 520                 525             


Glu Gln Lys 
    530     


<210>  17
<211>  321
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BC) 
       R88Q]

<400>  17

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


Pro 
    


<210>  18
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A)]

<400>  18

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ile Thr Leu Gln Glu Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  19
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A) E9A]

<400>  19

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ile Thr Leu Gln Ala Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  20
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A) I5A 
       E9Q]

<400>  20

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ala Thr Leu Gln Gln Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  21
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A) T6D 
       E9Q]

<400>  21

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ile Asp Leu Gln Gln Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  22
<211>  250
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (A) T6D 
       E9A]

<400>  22

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser His Lys Ser Asp Ile Asp Leu Gln Ala Ile Ile 
225                 230                 235                 240 


Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
                245                 250 


<210>  23
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       R88A]

<400>  23

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Ala Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  24
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       R81E R88Q]

<400>  24

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Glu Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  25
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       K84E R88Q]

<400>  25

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Glu Arg Leu Asp Gln Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  26
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       R88Q N89A]

<400>  26

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Ala Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  27
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BCD) 
       R88Q W91A]

<400>  27

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Asn Leu Ala Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


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


Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Ser Ser Ser 
            340                 345                 350 


<210>  28
<211>  286
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Split interleukin-4 (DA) T6D
       E9A]

<400>  28

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn 
225                 230                 235                 240 


Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys 
                245                 250                 255     


Ser Ser Gly Gly Gly Ser Gly Gly Ser His Lys Cys Asp Ile Asp Leu 
            260                 265                 270         


Gln Ala Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys 
        275                 280                 285     


<210>  29
<211>  321
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]-[Linker]-[Split interleukin-4 (BC) 
       R81E R88Q]

<400>  29

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala 
                245                 250                 255     


Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val 
            260                 265                 270         


Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly 
        275                 280                 285             


Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Glu Phe Leu 
    290                 295                 300                 


Lys Arg Leu Asp Gln Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys 
305                 310                 315                 320 


Pro 
    


<210>  30
<211>  569
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Her2-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[Split interleukin-4 (BC)]

<400>  30

Glu Val Gln Leu Val 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 Asn Ile Lys Asp Thr 
            20                  25                  30          


Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


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


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


Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 
        275                 280                 285             


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


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


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


Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys Ala Tyr 
            340                 345                 350         


Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        355                 360                 365             


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
    370                 375                 380                 


Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 
385                 390                 395                 400 


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
                405                 410                 415     


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
            420                 425                 430         


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
        435                 440                 445             


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
    450                 455                 460                 


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser 
465                 470                 475                 480 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Leu Cys Thr Glu Leu 
                485                 490                 495     


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


Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His 
        515                 520                 525             


Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg 
    530                 535                 540                 


His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp 
545                 550                 555                 560 


Gly Leu Ala Gly Leu Asn Ser Cys Pro 
                565                 


<210>  31
<211>  529
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Her2-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[Split interleukin-4 (DA)]

<400>  31

Glu Val Gln Leu Val 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 Asn Ile Lys Asp Thr 
            20                  25                  30          


Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


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


Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
                245                 250                 255     


Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile 
            260                 265                 270         


Lys Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
        275                 280                 285             


Leu Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg 
    290                 295                 300                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
305                 310                 315                 320 


Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr 
                325                 330                 335     


Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gln 
            340                 345                 350         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
        355                 360                 365             


Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
    370                 375                 380                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
385                 390                 395                 400 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                405                 410                 415     


Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            420                 425                 430         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        435                 440                 445             


Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly 
    450                 455                 460                 


Gly Gly Ser Gly Gly Gly Gly Ser Val Lys Glu Ala Asn Gln Ser Thr 
465                 470                 475                 480 


Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr 
                485                 490                 495     


Ser Lys Cys Ser Ser Gly Gly Gly Ser Gly Gly Ser His Lys Cys Asp 
            500                 505                 510         


Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln 
        515                 520                 525             


Lys 
    


<210>  32
<211>  456
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VH_CH1_Dig-VL_CH3-Hole]

<400>  32

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


Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Asp Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


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


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


Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Leu Ala Trp Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
                245                 250                 255     


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Lys 
            260                 265                 270         


Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu 
        275                 280                 285             


Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg Phe 
    290                 295                 300                 


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
305                 310                 315                 320 


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr Leu 
                325                 330                 335     


Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gln Pro 
            340                 345                 350         


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
        355                 360                 365             


Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser 
    370                 375                 380                 


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val 
                405                 410                 415     


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
            420                 425                 430         


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        435                 440                 445             


Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455     


<210>  33
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VH_CH3-Knob-K370E]

<400>  33

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


Ser Val Lys Val Ser Cys Lys Ser Ser Gly Phe Asn Asn Lys Asp Thr 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Gly Phe Thr Lys Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


<210>  34
<211>  623
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[Interleukin-2v]

<400>  34

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


Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Asp Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


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


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


Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Leu Ala Trp Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


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


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


Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu 
        275                 280                 285             


Trp Val Ser Ser Ile Asn Ile Gly Ala Thr Tyr Ile Tyr Tyr Ala Asp 
    290                 295                 300                 


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


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


Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys Ala Tyr Tyr 
            340                 345                 350         


Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly 
        355                 360                 365             


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
    370                 375                 380                 


Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
385                 390                 395                 400 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                405                 410                 415     


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
            420                 425                 430         


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
        435                 440                 445             


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
    450                 455                 460                 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly 
465                 470                 475                 480 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Pro Ala Ser Ser Ser Thr 
                485                 490                 495     


Lys Lys Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met 
            500                 505                 510         


Ile Leu Asn Gly Ile Asn Asn Tyr Ser Lys Asn Pro Lys Leu Thr Arg 
        515                 520                 525             


Met Leu Thr Ala Lys Phe Ala Met Pro Lys Lys Ala Thr Glu Leu Lys 
    530                 535                 540                 


His Leu Gln Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu 
545                 550                 555                 560 


Asn Gly Ala Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile 
                565                 570                 575     


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


Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu 
        595                 600                 605             


Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile Ile Ser Thr Leu Thr 
    610                 615                 620             


<210>  35
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[IL-2R? extracellular domain 
       (A27 - D239)]

<400>  35

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Ala Val Asn Gly Thr Ser Gln Phe Thr Cys Phe 
225                 230                 235                 240 


Tyr Asn Ser Arg Ala Asn Ile Ser Cys Val Trp Ser Gln Asp Gly Ala 
                245                 250                 255     


Leu Gln Asp Thr Ser Cys Gln Val His Ala Trp Pro Asp Arg Arg Arg 
            260                 265                 270         


Trp Asn Gln Thr Cys Glu Leu Leu Pro Val Ser Gln Ala Ser Trp Ala 
        275                 280                 285             


Cys Asn Leu Ile Leu Gly Ala Pro Asp Ser Gln Lys Leu Thr Thr Val 
    290                 295                 300                 


Asp Ile Val Thr Leu Arg Val Leu Cys Arg Glu Gly Val Arg Trp Arg 
305                 310                 315                 320 


Val Met Ala Ile Gln Asp Phe Lys Pro Phe Glu Asn Leu Arg Leu Met 
                325                 330                 335     


Ala Pro Ile Ser Leu Gln Val Val His Val Glu Thr His Arg Cys Asn 
            340                 345                 350         


Ile Ser Trp Glu Ile Ser Gln Ala Ser His Tyr Phe Glu Arg His Leu 
        355                 360                 365             


Glu Phe Glu Ala Arg Thr Leu Ser Pro Gly His Thr Trp Glu Glu Ala 
    370                 375                 380                 


Pro Leu Leu Thr Leu Lys Gln Lys Gln Glu Trp Ile Cys Leu Glu Thr 
385                 390                 395                 400 


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


Gln Gly Glu Phe Thr Thr Trp Ser Pro Trp Ser Gln Pro Leu Ala Phe 
            420                 425                 430         


Arg Thr Lys Pro Ala Ala Leu Gly Lys Asp 
        435                 440         


<210>  36
<211>  461
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[Common gamma chain (?c) 
       extracellular domain (L23 - N254)]

<400>  36

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Leu Asn Thr Thr Ile Leu Thr Pro Asn Gly Asn 
225                 230                 235                 240 


Glu Asp Thr Thr Ala Asp Phe Phe Leu Thr Thr Met Pro Thr Asp Ser 
                245                 250                 255     


Leu Ser Val Ser Thr Leu Pro Leu Pro Glu Val Gln Cys Phe Val Phe 
            260                 265                 270         


Asn Val Glu Tyr Met Asn Cys Thr Trp Asn Ser Ser Ser Glu Pro Gln 
        275                 280                 285             


Pro Thr Asn Leu Thr Leu His Tyr Trp Tyr Lys Asn Ser Asp Asn Asp 
    290                 295                 300                 


Lys Val Gln Lys Cys Ser His Tyr Leu Phe Ser Glu Glu Ile Thr Ser 
305                 310                 315                 320 


Gly Cys Gln Leu Gln Lys Lys Glu Ile His Leu Tyr Gln Thr Phe Val 
                325                 330                 335     


Val Gln Leu Gln Asp Pro Arg Glu Pro Arg Arg Gln Ala Thr Gln Met 
            340                 345                 350         


Leu Lys Leu Gln Asn Leu Val Ile Pro Trp Ala Pro Glu Asn Leu Thr 
        355                 360                 365             


Leu His Lys Leu Ser Glu Ser Gln Leu Glu Leu Asn Trp Asn Asn Arg 
    370                 375                 380                 


Phe Leu Asn His Cys Leu Glu His Leu Val Gln Tyr Arg Thr Asp Trp 
385                 390                 395                 400 


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


Leu Pro Ser Val Asp Gly Gln Lys Arg Tyr Thr Phe Arg Val Arg Ser 
            420                 425                 430         


Arg Phe Asn Pro Leu Cys Gly Ser Ala Gln His Trp Ser Glu Trp Ser 
        435                 440                 445             


His Pro Ile His Trp Gly Ser Asn Thr Ser Lys Glu Asn 
    450                 455                 460     


<210>  37
<211>  689
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[IL-2R?_?c]

<400>  37

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Ala Val Asn Gly Thr Ser Gln Phe Thr Cys Phe 
225                 230                 235                 240 


Tyr Asn Ser Arg Ala Asn Ile Ser Cys Val Trp Ser Gln Asp Gly Ala 
                245                 250                 255     


Leu Gln Asp Thr Ser Cys Gln Val His Ala Trp Pro Asp Arg Arg Arg 
            260                 265                 270         


Trp Asn Gln Thr Cys Glu Leu Leu Pro Val Ser Gln Ala Ser Trp Ala 
        275                 280                 285             


Cys Asn Leu Ile Leu Gly Ala Pro Asp Ser Gln Lys Leu Thr Thr Val 
    290                 295                 300                 


Asp Ile Val Thr Leu Arg Val Leu Cys Arg Glu Gly Val Arg Trp Arg 
305                 310                 315                 320 


Val Met Ala Ile Gln Asp Phe Lys Pro Phe Glu Asn Leu Arg Leu Met 
                325                 330                 335     


Ala Pro Ile Ser Leu Gln Val Val His Val Glu Thr His Arg Cys Asn 
            340                 345                 350         


Ile Ser Trp Glu Ile Ser Gln Ala Ser His Tyr Phe Glu Arg His Leu 
        355                 360                 365             


Glu Phe Glu Ala Arg Thr Leu Ser Pro Gly His Thr Trp Glu Glu Ala 
    370                 375                 380                 


Pro Leu Leu Thr Leu Lys Gln Lys Gln Glu Trp Ile Cys Leu Glu Thr 
385                 390                 395                 400 


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


Gln Gly Glu Phe Thr Thr Trp Ser Pro Trp Ser Gln Pro Leu Ala Phe 
            420                 425                 430         


Arg Thr Lys Pro Ala Ala Leu Gly Lys Asp Gly Gly Gly Gly Ser Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Leu Asn Thr Thr Ile Leu Thr 
    450                 455                 460                 


Pro Asn Gly Asn Glu Asp Thr Thr Ala Asp Phe Phe Leu Thr Thr Met 
465                 470                 475                 480 


Pro Thr Asp Ser Leu Ser Val Ser Thr Leu Pro Leu Pro Glu Val Gln 
                485                 490                 495     


Cys Phe Val Phe Asn Val Glu Tyr Met Asn Cys Thr Trp Asn Ser Ser 
            500                 505                 510         


Ser Glu Pro Gln Pro Thr Asn Leu Thr Leu His Tyr Trp Tyr Lys Asn 
        515                 520                 525             


Ser Asp Asn Asp Lys Val Gln Lys Cys Ser His Tyr Leu Phe Ser Glu 
    530                 535                 540                 


Glu Ile Thr Ser Gly Cys Gln Leu Gln Lys Lys Glu Ile His Leu Tyr 
545                 550                 555                 560 


Gln Thr Phe Val Val Gln Leu Gln Asp Pro Arg Glu Pro Arg Arg Gln 
                565                 570                 575     


Ala Thr Gln Met Leu Lys Leu Gln Asn Leu Val Ile Pro Trp Ala Pro 
            580                 585                 590         


Glu Asn Leu Thr Leu His Lys Leu Ser Glu Ser Gln Leu Glu Leu Asn 
        595                 600                 605             


Trp Asn Asn Arg Phe Leu Asn His Cys Leu Glu His Leu Val Gln Tyr 
    610                 615                 620                 


Arg Thr Asp Trp Asp His Ser Trp Thr Glu Gln Ser Val Asp Tyr Arg 
625                 630                 635                 640 


His Lys Phe Ser Leu Pro Ser Val Asp Gly Gln Lys Arg Tyr Thr Phe 
                645                 650                 655     


Arg Val Arg Ser Arg Phe Asn Pro Leu Cys Gly Ser Ala Gln His Trp 
            660                 665                 670         


Ser Glu Trp Ser His Pro Ile His Trp Gly Ser Asn Thr Ser Lys Glu 
        675                 680                 685             


Asn 
    


<210>  38
<211>  689
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[IL-12 p35 (C73S)]

<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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


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


Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
            260                 265                 270         


Thr Phe Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys 
        275                 280                 285             


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


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


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


Ala Val Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys 
            340                 345                 350         


Ala Tyr Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val 
        355                 360                 365             


Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro 
                485                 490                 495     


Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln 
            500                 505                 510         


Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr 
        515                 520                 525             


Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile 
    530                 535                 540                 


Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu 
545                 550                 555                 560 


Thr Lys Asn Glu Ser Ser Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr 
                565                 570                 575     


Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu 
            580                 585                 590         


Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe 
        595                 600                 605             


Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe 
    610                 615                 620                 


Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu 
625                 630                 635                 640 


Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro 
                645                 650                 655     


Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe 
            660                 665                 670         


Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala 
        675                 680                 685             


Ser 
    


<210>  39
<211>  777
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[IL-12 p40 (C177S)]

<400>  39

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


Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Asp Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


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


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


Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Leu Ala Trp Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
                245                 250                 255     


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Lys 
            260                 265                 270         


Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu 
        275                 280                 285             


Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro Ser Arg Phe 
    290                 295                 300                 


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
305                 310                 315                 320 


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ile Thr Leu 
                325                 330                 335     


Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gln Pro 
            340                 345                 350         


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
        355                 360                 365             


Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser 
    370                 375                 380                 


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val 
                405                 410                 415     


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
            420                 425                 430         


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        435                 440                 445             


Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly 
    450                 455                 460                 


Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr 
465                 470                 475                 480 


Val Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val 
                485                 490                 495     


Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp 
            500                 505                 510         


Gln Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val 
        515                 520                 525             


Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu 
    530                 535                 540                 


Val Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile 
545                 550                 555                 560 


Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr 
                565                 570                 575     


Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp 
            580                 585                 590         


Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser 
        595                 600                 605             


Arg Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu 
    610                 615                 620                 


Ser Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val 
625                 630                 635                 640 


Glu Cys Gln Glu Asp Ser Ala Ser Pro Ala Ala Glu Glu Ser Leu Pro 
                645                 650                 655     


Ile Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr 
            660                 665                 670         


Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys 
        675                 680                 685             


Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser 
    690                 695                 700                 


Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu 
705                 710                 715                 720 


Thr Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp 
                725                 730                 735     


Arg Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn 
            740                 745                 750         


Ala Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp 
        755                 760                 765             


Ser Glu Trp Ala Ser Val Pro Cys Ser 
    770                 775         


<210>  40
<211>  686
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [LeY-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[IL-12 p35 (C73S)]

<400>  40

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


Ser Leu Lys Leu Ser Cys Ala Thr Ser Gly Phe Thr Phe Ser Asp Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val 
        35                  40                  45              


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


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


Leu Gln Met Ser Arg Leu Lys Ser Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Leu Ala Trp Gly Ala Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


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


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


Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu 
        275                 280                 285             


Trp Val Ser Ser Ile Asn Ile Gly Ala Thr Tyr Ile Tyr Tyr Ala Asp 
    290                 295                 300                 


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


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


Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys Ala Tyr Tyr 
            340                 345                 350         


Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly 
        355                 360                 365             


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
    370                 375                 380                 


Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
385                 390                 395                 400 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                405                 410                 415     


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
            420                 425                 430         


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
        435                 440                 445             


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
    450                 455                 460                 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly 
465                 470                 475                 480 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr 
                485                 490                 495     


Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu 
            500                 505                 510         


Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe 
        515                 520                 525             


Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp 
    530                 535                 540                 


Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn 
545                 550                 555                 560 


Glu Ser Ser Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser 
                565                 570                 575     


Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser 
            580                 585                 590         


Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met 
        595                 600                 605             


Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln 
    610                 615                 620                 


Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn 
625                 630                 635                 640 


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


Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg 
            660                 665                 670         


Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
        675                 680                 685     


<210>  41
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [Biotin-VL_CH3-Hole-E357K]-[Linker]-[IL-12 p40i (C177S)]

<400>  41

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          


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


Tyr Ser Ala Lys Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Ser Ile Tyr 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 


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


Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg 
                245                 250                 255     


Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser 
            260                 265                 270         


Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly 
        275                 280                 285             


Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr 
    290                 295                 300                 


Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Ser Pro Ala Ala Glu 
305                 310                 315                 320 


Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys Leu Lys 
                325                 330                 335     


Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro 
            340                 345                 350         


Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln 
        355                 360                 365             


Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser 
    370                 375                 380                 


Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg 
385                 390                 395                 400 


Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile 
                405                 410                 415     


Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr 
            420                 425                 430         


Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser 
        435                 440                 445 


<210>  42
<211>  503
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VH_CH3-Knob]-[Linker]-[SmBiT]

<400>  42

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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


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


Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
            260                 265                 270         


Thr Phe Ser Asp Tyr Ala Met Ser Trp Ile Arg Gln Ala Pro Gly Lys 
        275                 280                 285             


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


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


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


Ala Val Tyr Tyr Cys Ala Arg Pro Gly Ser Pro Tyr Glu Tyr Asp Lys 
            340                 345                 350         


Ala Tyr Tyr Ser Met Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val 
        355                 360                 365             


Ser Ser Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Val Thr Gly Tyr 
                485                 490                 495     


Arg Leu Phe Glu Glu Ile Leu 
            500             


<210>  43
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [NADA-VL_CH3-Hole-E357K]

<400>  43

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


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


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


Gly Ser Ala Ser Gly Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ala Ser Gly Gly Ser 
                85                  90                  95      


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


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Lys Leu Thr Lys Asn 
        115                 120                 125             


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


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
145                 150                 155                 160 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
                165                 170                 175     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            180                 185                 190         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        195                 200                 205             


Ser Leu Ser Pro Gly Lys 
    210                 


<210>  44
<211>  633
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [CD38-VH_CH1_Dig-VL_CH3-Hole]-[Linker]-[LgBiT]

<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 Val Ser Gly Phe Thr Phe Asn Ser Phe 
            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 Gly 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 Phe Cys 
                85                  90                  95      


Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp 
            100                 105                 110         


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


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


Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
225                 230                 235                 240 


Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 
                245                 250                 255     


Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln 
            260                 265                 270         


Asp Ile Lys Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 
        275                 280                 285             


Pro Lys Leu Leu Ile Tyr Tyr Ser Ser Thr Leu Leu Ser Gly Val Pro 
    290                 295                 300                 


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
305                 310                 315                 320 


Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser 
                325                 330                 335     


Ile Thr Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            340                 345                 350         


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
        355                 360                 365             


Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 
    370                 375                 380                 


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
385                 390                 395                 400 


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


Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
            420                 425                 430         


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
        435                 440                 445             


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser 
    450                 455                 460                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Val Phe Thr Leu Glu 
465                 470                 475                 480 


Asp Phe Val Gly Asp Trp Glu Gln Thr Ala Ala Tyr Asn Leu Asp Gln 
                485                 490                 495     


Val Leu Glu Gln Gly Gly Val Ser Ser Leu Leu Gln Asn Leu Ala Val 
            500                 505                 510         


Ser Val Thr Pro Ile Gln Arg Ile Val Arg Ser Gly Glu Asn Ala Leu 
        515                 520                 525             


Lys Ile Asp Ile His Val Ile Ile Pro Tyr Glu Gly Leu Ser Ala Asp 
    530                 535                 540                 


Gln Met Ala Gln Ile Glu Glu Val Phe Lys Val Val Tyr Pro Val Asp 
545                 550                 555                 560 


Asp His His Phe Lys Val Ile Leu Pro Tyr Gly Thr Leu Val Ile Asp 
                565                 570                 575     


Gly Val Thr Pro Asn Met Leu Asn Tyr Phe Gly Arg Pro Tyr Glu Gly 
            580                 585                 590         


Ile Ala Val Phe Asp Gly Lys Lys Ile Thr Val Thr Gly Thr Leu Trp 
        595                 600                 605             


Asn Gly Asn Lys Ile Ile Asp Glu Arg Leu Ile Thr Pro Asp Gly Ser 
    610                 615                 620                 


Met Leu Phe Arg Val Thr Ile Asn Ser 
625                 630             


<210>  45
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  [NADA-VH_CH3-Knob-K370E]

<400>  45

Glu Val Gln Leu Val 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 Ser Ile Ala Gly Thr 
            20                  25                  30          


Ala Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


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


Ser Arg Ser Gly Gly Ser Gly Ala Ser Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


