                         SEQUENCE LISTING

<110>  OSE IMMUNOTHERAPEUTICS
 
<120>  NEW SCAFFOLD FOR BIFUNCTIONAL MOLECULES WITH IMPROVED PROPERTIES

<130>  B3521PC

<160>  87    

<170>  PatentIn version 3.5

<210>  1
<211>  343
<212>  PRT
<213>  artificial

<220>
<223>  extracellular SIRPA

<400>  1

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


Ala Gly Glu Thr Ala Thr Leu Arg Cys Thr Ala Thr Ser Leu Ile Pro 
            20                  25                  30          


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


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


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


Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys 
                85                  90                  95      


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


Ser Val Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala 
        115                 120                 125             


Arg Ala Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly 
    130                 135                 140                 


Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu 
145                 150                 155                 160 


Leu Ser Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser 
                165                 170                 175     


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


His Ser Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp 
        195                 200                 205             


Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro 
    210                 215                 220                 


Thr Leu Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn 
225                 230                 235                 240 


Val Thr Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr 
                245                 250                 255     


Trp Leu Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val 
            260                 265                 270         


Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val 
        275                 280                 285             


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


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


Ala His Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly 
                325                 330                 335     


Ser Asn Glu Arg Asn Ile Tyr 
            340             


<210>  2
<211>  332
<212>  PRT
<213>  artificial

<220>
<223>  extracellular SIRPG

<400>  2

Glu Glu Glu Leu Gln Met Ile Gln Pro Glu Lys Leu Leu Leu Val Thr 
1               5                   10                  15      


Val Gly Lys Thr Ala Thr Leu His Cys Thr Val Thr Ser Leu Leu Pro 
            20                  25                  30          


Val Gly Pro Val Leu Trp Phe Arg Gly Val Gly Pro Gly Arg Glu Leu 
        35                  40                  45              


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


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


Ile Thr Pro Ala Asp Val Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys 
                85                  90                  95      


Gly Ser Pro Glu Asn Val Glu Phe Lys Ser Gly Pro Gly Thr Glu Met 
            100                 105                 110         


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


Arg Thr Thr Pro Glu His Thr Val Ser Phe Thr Cys Glu Ser His Gly 
    130                 135                 140                 


Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu 
145                 150                 155                 160 


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


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


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


Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Ala Ile Arg Val Pro Pro 
    210                 215                 220                 


Thr Leu Glu Val Thr Gln Gln Pro Met Arg Val Gly Asn Gln Val Asn 
225                 230                 235                 240 


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


Trp Ser Glu Asn Gly Asn Val Cys Gln Arg Glu Thr Ala Ser Thr Leu 
            260                 265                 270         


Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Thr Ser Trp Phe Leu Val 
        275                 280                 285             


Asn Ile Ser Asp Gln Arg Asp Asp Val Val Leu Thr Cys Gln Val Lys 
    290                 295                 300                 


His Asp Gly Gln Leu Ala Val Ser Lys Arg Leu Ala Leu Glu Val Thr 
305                 310                 315                 320 


Val His Gln Lys Asp Gln Ser Ser Asp Ala Thr Pro 
                325                 330         


<210>  3
<211>  794
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD-1-CH1-KIH-FcG1m-(G4S)3-SIRPG (Hole)

<400>  3

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Met Ile Gln Pro Glu Lys Leu Leu Leu Val Thr Val Gly 
465                 470                 475                 480 


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


Pro Val Leu Trp Phe Arg Gly Val Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Ser Ser Ile Thr 
    530                 535                 540                 


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


Pro Glu Asn Val Glu Phe Lys Ser Gly Pro Gly Thr Glu Met Ala Leu 
                565                 570                 575     


Gly Ala Lys Pro Ser Ala Pro Val Val Leu Gly Pro Ala Ala Arg Thr 
            580                 585                 590         


Thr Pro Glu His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Thr Gly Gln Ser Val Ala Tyr Ser 
625                 630                 635                 640 


Ile Arg Ser Thr Ala Arg Val Val Leu Asp Pro Trp Asp Val Arg Ser 
                645                 650                 655     


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Ala Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Met Arg Val Gly Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Ser Leu Gln Leu Thr Trp Ser 
705                 710                 715                 720 


Glu Asn Gly Asn Val Cys Gln Arg Glu Thr Ala Ser Thr Leu Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Thr Ser Trp Phe Leu Val Asn Ile 
            740                 745                 750         


Ser Asp Gln Arg Asp Asp Val Val Leu Thr Cys Gln Val Lys His Asp 
        755                 760                 765             


Gly Gln Leu Ala Val Ser Lys Arg Leu Ala Leu Glu Val Thr Val His 
    770                 775                 780                 


Gln Lys Asp Gln Ser Ser Asp Ala Thr Pro 
785                 790                 


<210>  4
<211>  794
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD1-FcG1m-(G4S)3-SIRPG

<400>  4

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


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


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Met Ile Gln Pro Glu Lys Leu Leu Leu Val Thr Val Gly 
465                 470                 475                 480 


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


Pro Val Leu Trp Phe Arg Gly Val Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Ser Ser Ile Thr 
    530                 535                 540                 


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


Pro Glu Asn Val Glu Phe Lys Ser Gly Pro Gly Thr Glu Met Ala Leu 
                565                 570                 575     


Gly Ala Lys Pro Ser Ala Pro Val Val Leu Gly Pro Ala Ala Arg Thr 
            580                 585                 590         


Thr Pro Glu His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Thr Gly Gln Ser Val Ala Tyr Ser 
625                 630                 635                 640 


Ile Arg Ser Thr Ala Arg Val Val Leu Asp Pro Trp Asp Val Arg Ser 
                645                 650                 655     


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Ala Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Met Arg Val Gly Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Ser Leu Gln Leu Thr Trp Ser 
705                 710                 715                 720 


Glu Asn Gly Asn Val Cys Gln Arg Glu Thr Ala Ser Thr Leu Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Thr Ser Trp Phe Leu Val Asn Ile 
            740                 745                 750         


Ser Asp Gln Arg Asp Asp Val Val Leu Thr Cys Gln Val Lys His Asp 
        755                 760                 765             


Gly Gln Leu Ala Val Ser Lys Arg Leu Ala Leu Glu Val Thr Val His 
    770                 775                 780                 


Gln Lys Asp Gln Ser Ser Asp Ala Thr Pro 
785                 790                 


<210>  5
<211>  805
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD1-FcG1m-(G4S)3-SIRPA

<400>  5

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


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


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Val Ile Gln Pro Asp Lys Ser Val Leu Val Ala Ala Gly 
465                 470                 475                 480 


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


Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn Ile Thr 
    530                 535                 540                 


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


Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu Ser Val 
                565                 570                 575     


Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala Arg Ala 
            580                 585                 590         


Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser Tyr Ser 
625                 630                 635                 640 


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


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu 
705                 710                 715                 720 


Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val Asn Val 
            740                 745                 750         


Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu His Asp 
        755                 760                 765             


Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser Ala His 
    770                 775                 780                 


Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn 
785                 790                 795                 800 


Glu Arg Asn Ile Tyr 
                805 


<210>  6
<211>  805
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD1-KIH-FcG1m-(G4S)3-SIRPA (Hole)

<400>  6

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Val Ile Gln Pro Asp Lys Ser Val Leu Val Ala Ala Gly 
465                 470                 475                 480 


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


Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn Ile Thr 
    530                 535                 540                 


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


Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu Ser Val 
                565                 570                 575     


Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala Arg Ala 
            580                 585                 590         


Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser Tyr Ser 
625                 630                 635                 640 


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


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu 
705                 710                 715                 720 


Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val Asn Val 
            740                 745                 750         


Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu His Asp 
        755                 760                 765             


Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser Ala His 
    770                 775                 780                 


Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn 
785                 790                 795                 800 


Glu Arg Asn Ile Tyr 
                805 


<210>  7
<211>  566
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD1-LC-SIRPG

<400>  7

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Thr His Val Pro Asn Thr Phe Gly Gln 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 Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu Glu Leu Gln Met 
225                 230                 235                 240 


Ile Gln Pro Glu Lys Leu Leu Leu Val Thr Val Gly Lys Thr Ala Thr 
                245                 250                 255     


Leu His Cys Thr Val Thr Ser Leu Leu Pro Val Gly Pro Val Leu Trp 
            260                 265                 270         


Phe Arg Gly Val Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu 
        275                 280                 285             


Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn 
    290                 295                 300                 


Asn Met Asp Phe Ser Ile Arg Ile Ser Ser Ile Thr Pro Ala Asp Val 
305                 310                 315                 320 


Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys Gly Ser Pro Glu Asn Val 
                325                 330                 335     


Glu Phe Lys Ser Gly Pro Gly Thr Glu Met Ala Leu Gly Ala Lys Pro 
            340                 345                 350         


Ser Ala Pro Val Val Leu Gly Pro Ala Ala Arg Thr Thr Pro Glu His 
        355                 360                 365             


Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser Pro Arg Asp Ile 
    370                 375                 380                 


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


Asn Val Asp Pro Thr Gly Gln Ser Val Ala Tyr Ser Ile Arg Ser Thr 
                405                 410                 415     


Ala Arg Val Val Leu Asp Pro Trp Asp Val Arg Ser Gln Val Ile Cys 
            420                 425                 430         


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


Asn Leu Ser Glu Ala Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln 
    450                 455                 460                 


Gln Pro Met Arg Val Gly Asn Gln Val Asn Val Thr Cys Gln Val Arg 
465                 470                 475                 480 


Lys Phe Tyr Pro Gln Ser Leu Gln Leu Thr Trp Ser Glu Asn Gly Asn 
                485                 490                 495     


Val Cys Gln Arg Glu Thr Ala Ser Thr Leu Thr Glu Asn Lys Asp Gly 
            500                 505                 510         


Thr Tyr Asn Trp Thr Ser Trp Phe Leu Val Asn Ile Ser Asp Gln Arg 
        515                 520                 525             


Asp Asp Val Val Leu Thr Cys Gln Val Lys His Asp Gly Gln Leu Ala 
    530                 535                 540                 


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


Ser Ser Asp Ala Thr Pro 
                565     


<210>  8
<211>  577
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD1-LC-SIRPA

<400>  8

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Thr His Val Pro Asn Thr Phe Gly Gln 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 Gly Gly Gly Gly Ser 
    210                 215                 220                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu Glu Leu Gln Val 
225                 230                 235                 240 


Ile Gln Pro Asp Lys Ser Val Leu Val Ala Ala Gly Glu Thr Ala Thr 
                245                 250                 255     


Leu Arg Cys Thr Ala Thr Ser Leu Ile Pro Val Gly Pro Ile Gln Trp 
            260                 265                 270         


Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu 
        275                 280                 285             


Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn 
    290                 295                 300                 


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


Gly Thr Tyr Tyr Cys Val Lys Phe Arg Lys Gly Ser Pro Asp Asp Val 
                325                 330                 335     


Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu Ser Val Arg Ala Lys Pro 
            340                 345                 350         


Ser Ala Pro Val Val Ser Gly Pro Ala Ala Arg Ala Thr Pro Gln His 
        355                 360                 365             


Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser Pro Arg Asp Ile 
    370                 375                 380                 


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


Asn Val Asp Pro Val Gly Glu Ser Val Ser Tyr Ser Ile His Ser Thr 
                405                 410                 415     


Ala Lys Val Val Leu Thr Arg Glu Asp Val His Ser Gln Val Ile Cys 
            420                 425                 430         


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


Asn Leu Ser Glu Thr Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln 
    450                 455                 460                 


Gln Pro Val Arg Ala Glu Asn Gln Val Asn Val Thr Cys Gln Val Arg 
465                 470                 475                 480 


Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu Glu Asn Gly Asn 
                485                 490                 495     


Val Ser Arg Thr Glu Thr Ala Ser Thr Val Thr Glu Asn Lys Asp Gly 
            500                 505                 510         


Thr Tyr Asn Trp Met Ser Trp Leu Leu Val Asn Val Ser Ala His Arg 
        515                 520                 525             


Asp Asp Val Lys Leu Thr Cys Gln Val Glu His Asp Gly Gln Pro Ala 
    530                 535                 540                 


Val Ser Lys Ser His Asp Leu Lys Val Ser Ala His Pro Lys Glu Gln 
545                 550                 555                 560 


Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn Glu Arg Asn Ile 
                565                 570                 575     


Tyr 
    


<210>  9
<211>  447
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD-1-CH1-KIH-FcG1m (Hole)

<400>  9

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445         


<210>  10
<211>  447
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD-1-CH1-KIH-FcG1m (Knob)

<400>  10

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445         


<210>  11
<211>  219
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD-1-CL

<400>  11

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Thr His Val Pro Asn Thr Phe Gly Gln 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>  12
<211>  220
<212>  PRT
<213>  artificial

<220>
<223>  Anti-PD-1-CH1

<400>  12

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


<210>  13
<211>  227
<212>  PRT
<213>  artificial

<220>
<223>  KIH-FcG1m (Hole)

<400>  13

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


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


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


Leu Ser Cys Ala Val Lys 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 Val 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>  14
<211>  227
<212>  PRT
<213>  artificial

<220>
<223>  KIH-FcG1m (Knob)

<400>  14

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


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


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


Leu Trp Cys Leu Val Lys 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>  15
<211>  794
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD1-KIH-FcG1m-(G4S)3-SIRPG (knob)

<400>  15

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Met Ile Gln Pro Glu Lys Leu Leu Leu Val Thr Val Gly 
465                 470                 475                 480 


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


Pro Val Leu Trp Phe Arg Gly Val Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Ser Ser Ile Thr 
    530                 535                 540                 


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


Pro Glu Asn Val Glu Phe Lys Ser Gly Pro Gly Thr Glu Met Ala Leu 
                565                 570                 575     


Gly Ala Lys Pro Ser Ala Pro Val Val Leu Gly Pro Ala Ala Arg Thr 
            580                 585                 590         


Thr Pro Glu His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Thr Gly Gln Ser Val Ala Tyr Ser 
625                 630                 635                 640 


Ile Arg Ser Thr Ala Arg Val Val Leu Asp Pro Trp Asp Val Arg Ser 
                645                 650                 655     


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Ala Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Met Arg Val Gly Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Ser Leu Gln Leu Thr Trp Ser 
705                 710                 715                 720 


Glu Asn Gly Asn Val Cys Gln Arg Glu Thr Ala Ser Thr Leu Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Thr Ser Trp Phe Leu Val Asn Ile 
            740                 745                 750         


Ser Asp Gln Arg Asp Asp Val Val Leu Thr Cys Gln Val Lys His Asp 
        755                 760                 765             


Gly Gln Leu Ala Val Ser Lys Arg Leu Ala Leu Glu Val Thr Val His 
    770                 775                 780                 


Gln Lys Asp Gln Ser Ser Asp Ala Thr Pro 
785                 790                 


<210>  16
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  LC CDR3

<400>  16

Phe Gln Gly Thr His Val Pro Asn Thr 
1               5                   


<210>  17
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain


<220>
<221>  MISC_FEATURE
<222>  (105)..(105)
<223>  X is X1, D or E

<220>
<221>  MISC_FEATURE
<222>  (106)..(106)
<223>  X is X2, and is T, H, A, Y, N, E or S

<400>  17

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Xaa Xaa Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  18
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  18

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Ser Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  19
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  19

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Thr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  20
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  20

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Glu Ser Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  21
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  21

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp His Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  22
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  22

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Ala Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  23
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  23

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  24
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  24

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  25
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  HC variable domain

<400>  25

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Glu Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  26
<211>  112
<212>  PRT
<213>  artificial

<220>
<223>  LC variable domain


<220>
<221>  MISC_FEATURE
<222>  (34)..(34)
<223>  X is G or T

<400>  26

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


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


<210>  27
<211>  112
<212>  PRT
<213>  artificial

<220>
<223>  LC variable domain

<400>  27

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


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


<210>  28
<211>  112
<212>  PRT
<213>  artificial

<220>
<223>  LC variable domain

<400>  28

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


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


<210>  29
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  29

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Ser Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  30
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  30

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Thr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  31
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  31

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Glu Ser Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  32
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  32

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp His Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  33
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  33

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Ala Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  34
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  34

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  35
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  35

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  36
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC

<400>  36

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Glu Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  37
<211>  219
<212>  PRT
<213>  artificial

<220>
<223>  LC

<400>  37

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Thr His Val Pro Asn Thr Phe Gly Gln 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>  38
<211>  219
<212>  PRT
<213>  artificial

<220>
<223>  LC

<400>  38

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


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


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


Pro Arg 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 Val Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Thr His Val Pro Asn Thr Phe Gly Gln 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>  39
<211>  327
<212>  PRT
<213>  artificial

<220>
<223>  HC constant domain

<400>  39

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
1               5                   10                  15      


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


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
65                  70                  75                  80  


Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                165                 170                 175     


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
        195                 200                 205             


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
225                 230                 235                 240 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             


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


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
305                 310                 315                 320 


Leu Ser Leu Ser Pro Gly Lys 
                325         


<210>  40
<211>  107
<212>  PRT
<213>  artificial

<220>
<223>  LC contant domain

<400>  40

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
            20                  25                  30          


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  41
<211>  30
<212>  PRT
<213>  artificial

<220>
<223>  HFR1

<400>  41

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr 
            20                  25                  30  


<210>  42
<211>  14
<212>  PRT
<213>  artificial

<220>
<223>  HFR2

<400>  42

Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly 
1               5                   10                  


<210>  43
<211>  32
<212>  PRT
<213>  artificial

<220>
<223>  HFR3

<400>  43

Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr Leu Gln 
1               5                   10                  15      


Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
            20                  25                  30          


<210>  44
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  HFR4

<400>  44

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
1               5                   10      


<210>  45
<211>  23
<212>  PRT
<213>  artificial

<220>
<223>  LFR1

<400>  45

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


Gln Pro Ala Ser Ile Ser Cys 
            20              


<210>  46
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  LFR2

<400>  46

Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr 
1               5                   10                  15  


<210>  47
<211>  32
<212>  PRT
<213>  artificial

<220>
<223>  LFR3

<400>  47

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
1               5                   10                  15      


Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys 
            20                  25                  30          


<210>  48
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  LFR4

<400>  48

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
1               5                   10  


<210>  49
<211>  19
<212>  PRT
<213>  artificial

<220>
<223>  signal peptide

<400>  49

Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gln Ser 
1               5                   10                  15      


Ile Gln Ala 
            


<210>  50
<211>  19
<212>  PRT
<213>  artificial

<220>
<223>  signal peptide

<400>  50

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala 
1               5                   10                  15      


Ser Ser Ser 
            


<210>  51
<211>  5
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR1

<400>  51

His Tyr Ala Met Asn 
1               5   


<210>  52
<211>  330
<212>  PRT
<213>  artificial

<220>
<223>  Heavy chain constant domain (IgG1m-N298A)

<400>  52

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      


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


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    130                 135                 140                 


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
225                 230                 235                 240 


Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                245                 250                 255     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  53
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR2

<400>  53

Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe Thr 
1               5                   10                  15      


Gly 
    


<210>  54
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  X is X1 (D or E)

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  X is X2 and is T, H, A, Y, N, E or S

<400>  54

Glu Arg Glu Pro Gly Met Xaa Xaa 
1               5               


<210>  55
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  55

Glu Arg Glu Pro Gly Met Asp Ser 
1               5               


<210>  56
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  56

Glu Arg Glu Pro Gly Met Asp Thr 
1               5               


<210>  57
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  57

Glu Arg Glu Pro Gly Met Glu Ser 
1               5               


<210>  58
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  58

Glu Arg Glu Pro Gly Met Asp His 
1               5               


<210>  59
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  59

Glu Arg Glu Pro Gly Met Asp Ala 
1               5               


<210>  60
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  60

Glu Arg Glu Pro Gly Met Asp Tyr 
1               5               


<210>  61
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  61

Glu Arg Glu Pro Gly Met Asp Asn 
1               5               


<210>  62
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  HC CDR3

<400>  62

Glu Arg Glu Pro Gly Met Asp Glu 
1               5               


<210>  63
<211>  16
<212>  PRT
<213>  artificial

<220>
<223>  LC CDR1


<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  X is G or T

<400>  63

Arg Ser Ser Gln Ser Leu Val His Ala Asn Xaa Asn Thr Tyr Leu Glu 
1               5                   10                  15      


<210>  64
<211>  16
<212>  PRT
<213>  artificial

<220>
<223>  LC CDR1

<400>  64

Arg Ser Ser Gln Ser Leu Val His Ala Asn Gly Asn Thr Tyr Leu Glu 
1               5                   10                  15      


<210>  65
<211>  16
<212>  PRT
<213>  artificial

<220>
<223>  LC CDR1

<400>  65

Arg Ser Ser Gln Ser Leu Val His Ala Asn Thr Asn Thr Tyr Leu Glu 
1               5                   10                  15      


<210>  66
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  LC CDR2

<400>  66

Lys Val Ser Asn Arg Phe Ser 
1               5           


<210>  67
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  linker C

<400>  67

Gly Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   


<210>  68
<211>  5
<212>  PRT
<213>  artificial

<220>
<223>  linker G4S

<400>  68

Gly Gly Gly Gly Ser 
1               5   


<210>  69
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  linker (G4S)2

<400>  69

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


<210>  70
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  linker (G4S)3

<400>  70

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


<210>  71
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  HC anti-PD1 chimeric

<400>  71

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


Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met 
        35                  40                  45              


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Glu Glu Phe 
    50                  55                  60                  


Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Ala Ala Phe 
65                  70                  75                  80  


Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Tyr Phe Cys 
                85                  90                  95      


Ala Lys Glu Arg Glu Pro Gly Met Asp Ser Trp Gly Gln Gly Thr Ser 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  72
<211>  219
<212>  PRT
<213>  artificial

<220>
<223>  LC anti-PD1 chimeric

<400>  72

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Asn Ile Val His Ala 
            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  


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


Ser His Val Pro Asn Thr Phe Gly Gly 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>  73
<211>  2670
<212>  DNA
<213>  artificial

<220>
<223>  VH-VK

<400>  73
cagatccagc tggtgcagag cggctctgag ctgaagaagc caggcgcttc tgtgaaggtg       60

tcctgcaagg ccagcggcta caccttcaca cactatgcta tgaattgggt gagacaggct      120

ccaggacagg gactggagtg gatgggctgg atcaacacca atacaggcga gcctacctac      180

gctcagggct ttacaggccg cttcgtgttt tctctggata cctccgtgag cacagcctat      240

ctgcagatct ccagcctgaa ggctgaggac accgccgtgt actattgtgc tagggagagg      300

gagccaggaa tggataactg gggacagggc accctggtga cagtgtcttc cgctagcacc      360

aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc      420

gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca      480

ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac      540

tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc      600

aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt      660

cccccatgcc caccatgccc agcacctgag ttcctggggg gaccatcagt cttcctgttc      720

cccccaaaac ccaaggacac tctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg      780

gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag      840

gtgcataatg ccaagacaaa gccgcgggag gagcagttca acagcacgta ccgtgtggtc      900

agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc      960

tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc     1020

cgagagccac aggtgtacac cctgccccca tcccaggagg agatgaccaa gaaccaggtc     1080

agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc     1140

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc     1200

ttcttcctct acagcaggct aaccgtggac aagagcaggt ggcaggaggg gaatgtcttc     1260

tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagag cctctccctg     1320

tctccgggta aatgacagat ccagctggtg cagagcggct ctgagctgaa gaagccaggc     1380

gcttctgtga aggtgtcctg caaggccagc ggctacacct tcacacacta tgctatgaat     1440

tgggtgagac aggctccagg acagggactg gagtggatgg gctggatcaa caccaataca     1500

ggcgagccta cctacgctca gggctttaca ggccgcttcg tgttttctct ggatacctcc     1560

gtgagcacag cctatctgca gatctccagc ctgaaggctg aggacaccgc cgtgtactat     1620

tgtgctaggg agagggagcc aggaatggat aactggggac agggcaccct ggtgacagtg     1680

tcttccgcta gcaccaaggg cccatcggtc ttccccctgg cgccctgctc caggagcacc     1740

tccgagagca cagccgccct gggctgcctg gtcaaggact acttccccga accggtgacg     1800

gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag     1860

tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacg     1920

aagacctaca cctgcaacgt agatcacaag cccagcaaca ccaaggtgga caagagagtt     1980

gagtccaaat atggtccccc atgcccacca tgcccagcac ctgagttcct ggggggacca     2040

tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag     2100

gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac     2160

gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc     2220

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa cggcaaggag     2280

tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa     2340

gccaaagggc agccccgaga gccacaggtg tacaccctgc ccccatccca ggaggagatg     2400

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc     2460

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg     2520

gactccgacg gctccttctt cctctacagc aggctaaccg tggacaagag caggtggcag     2580

gaggggaatg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacacag     2640

aagagcctct ccctgtctcc gggtaaatga                                      2670


<210>  74
<211>  660
<212>  DNA
<213>  artificial

<220>
<223>  VL-VD

<400>  74
gacgtggtca tgacacagag cccactgtct ctgcctgtga ccctgggaca gccagcctct       60

atctcctgca gatccagcca gtctctggtg cacgctaaca ccaatacata cctggagtgg      120

tatcagcaga ggccaggaca gtccccaagg ctgctgatct acaaggtgtc caacagattc      180

agcggagtgc cagaccgctt tagcggatct ggatccggaa ccgacttcac cctgaagatc      240

tccagggtgg aggctgagga tgtgggcgtg tactattgtt tccagggcac ccatgtgcct      300

aatacatttg gccagggcac caagctggag atcaagcgta cggtggctgc accatctgtc      360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg      420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa      480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc      540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa      600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgttag      660


<210>  75
<211>  805
<212>  PRT
<213>  artificial

<220>
<223>  anti-PD1-KIH-FcG1m-(G4S)3-SIRPA (knob)

<400>  75

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Asn Thr Gly Glu Pro Thr Tyr Ala Gln Gly Phe 
    50                  55                  60                  


Thr Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Arg Glu Pro Gly Met Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
        355                 360                 365             


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


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


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


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly 
        435                 440                 445             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu 
    450                 455                 460                 


Glu Leu Gln Val Ile Gln Pro Asp Lys Ser Val Leu Val Ala Ala Gly 
465                 470                 475                 480 


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


Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr 
            500                 505                 510         


Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser Asp Leu 
        515                 520                 525             


Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn Ile Thr 
    530                 535                 540                 


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


Pro Asp Asp Val Glu Phe Lys Ser Gly Ala Gly Thr Glu Leu Ser Val 
                565                 570                 575     


Arg Ala Lys Pro Ser Ala Pro Val Val Ser Gly Pro Ala Ala Arg Ala 
            580                 585                 590         


Thr Pro Gln His Thr Val Ser Phe Thr Cys Glu Ser His Gly Phe Ser 
        595                 600                 605             


Pro Arg Asp Ile Thr Leu Lys Trp Phe Lys Asn Gly Asn Glu Leu Ser 
    610                 615                 620                 


Asp Phe Gln Thr Asn Val Asp Pro Val Gly Glu Ser Val Ser Tyr Ser 
625                 630                 635                 640 


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


Gln Val Ile Cys Glu Val Ala His Val Thr Leu Gln Gly Asp Pro Leu 
            660                 665                 670         


Arg Gly Thr Ala Asn Leu Ser Glu Thr Ile Arg Val Pro Pro Thr Leu 
        675                 680                 685             


Glu Val Thr Gln Gln Pro Val Arg Ala Glu Asn Gln Val Asn Val Thr 
    690                 695                 700                 


Cys Gln Val Arg Lys Phe Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu 
705                 710                 715                 720 


Glu Asn Gly Asn Val Ser Arg Thr Glu Thr Ala Ser Thr Val Thr Glu 
                725                 730                 735     


Asn Lys Asp Gly Thr Tyr Asn Trp Met Ser Trp Leu Leu Val Asn Val 
            740                 745                 750         


Ser Ala His Arg Asp Asp Val Lys Leu Thr Cys Gln Val Glu His Asp 
        755                 760                 765             


Gly Gln Pro Ala Val Ser Lys Ser His Asp Leu Lys Val Ser Ala His 
    770                 775                 780                 


Pro Lys Glu Gln Gly Ser Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn 
785                 790                 795                 800 


Glu Arg Asn Ile Tyr 
                805 


<210>  76
<211>  120
<212>  PRT
<213>  artificial

<220>
<223>  VH anti-CD28
<400>  76

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          


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


Gly Cys Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asp Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  77
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  HCDR1 anti-CD28

<400>  77

Gly Tyr Thr Phe Thr Ser Tyr Tyr Ile His 
1               5                   10  


<210>  78
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  HCDR2 anti-CD28

<400>  78

Cys Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Asn Glu Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  79
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  HCDR3 anti-CD28

<400>  79

Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val 
1               5                   10      


<210>  80
<211>  107
<212>  PRT
<213>  artificial

<220>
<223>  VL anti-CD28

<400>  80

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 His Ala Ser Gln Asn Ile Tyr Val Trp 
            20                  25                  30          


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


Tyr Lys Ala Ser Asn Leu His Thr 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 Gly Gln Thr Tyr Pro Tyr 
                85                  90                  95      


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


<210>  81
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  LCDR1 anti-CD28

<400>  81

His Ala Ser Gln Asn Ile Tyr Val Trp Leu Asn 
1               5                   10      


<210>  82
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  LCDR2 anti-CD28

<400>  82

Lys Ala Ser Asn Leu His Thr 
1               5           


<210>  83
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  LCDR3 anti CD-28

<400>  83

Gln Gln Gly Gln Thr Tyr Pro Tyr Thr 
1               5                   


<210>  84
<211>  228
<212>  PRT
<213>  artificial

<220>
<223>  Fc chain (Knob)

<400>  84

Glu Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
1               5                   10                  15      


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            20                  25                  30          


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        35                  40                  45              


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    50                  55                  60                  


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
65                  70                  75                  80  


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                85                  90                  95      


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            100                 105                 110         


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


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


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


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


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


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


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


Ser Pro Gly Lys 
225             


<210>  85
<211>  459
<212>  PRT
<213>  artificial

<220>
<223>  Heavy chain (Hole)

<400>  85

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          


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


Gly Cys Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asp Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


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


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
    130                 135                 140                 


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
145                 150                 155                 160 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
                165                 170                 175     


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
            180                 185                 190         


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
        195                 200                 205             


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
    210                 215                 220                 


Phe Asn Arg Gly Glu Cys Leu Glu Asp Lys Thr His Thr Cys Pro Pro 
225                 230                 235                 240 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
                245                 250                 255     


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
            260                 265                 270         


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
        275                 280                 285             


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
    290                 295                 300                 


Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
305                 310                 315                 320 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
                325                 330                 335     


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
            340                 345                 350         


Gly Gln Pro Arg Glu Pro Gln Val Cys 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 
    450                 455                 


<210>  86
<211>  584
<212>  PRT
<213>  artificial

<220>
<223>  Light chain-SIRPa Bicki-CD28-SIRPa (monoTGN-SIRPa)

<400>  86

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 His Ala Ser Gln Asn Ile Tyr Val Trp 
            20                  25                  30          


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


Tyr Lys Ala Ser Asn Leu His Thr 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 Gly Gln Thr Tyr Pro Tyr 
                85                  90                  95      


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


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


Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
    130                 135                 140                 


Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
145                 150                 155                 160 


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


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


Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 
        195                 200                 205             


Pro Lys Ser Cys Asp Lys Ala Ala Ala Gly Gly Gly Gly Ser Gly Gly 
    210                 215                 220                 


Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu Glu Leu Gln Val Ile Gln 
225                 230                 235                 240 


Pro Asp Lys Ser Val Leu Val Ala Ala Gly Glu Thr Ala Thr Leu Arg 
                245                 250                 255     


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


Gly Ala Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu Gly His 
        275                 280                 285             


Phe Pro Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn Asn Met 
    290                 295                 300                 


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


Tyr Tyr Cys Val Lys Phe Arg Lys Gly Ser Pro Asp Asp Val Glu Phe 
                325                 330                 335     


Lys Ser Gly Ala Gly Thr Glu Leu Ser Val Arg Ala Lys Pro Ser Ala 
            340                 345                 350         


Pro Val Val Ser Gly Pro Ala Ala Arg Ala Thr Pro Gln His Thr Val 
        355                 360                 365             


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


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


Asp Pro Val Gly Glu Ser Val Ser Tyr Ser Ile His Ser Thr Ala Lys 
                405                 410                 415     


Val Val Leu Thr Arg Glu Asp Val His Ser Gln Val Ile Cys Glu Val 
            420                 425                 430         


Ala His Val Thr Leu Gln Gly Asp Pro Leu Arg Gly Thr Ala Asn Leu 
        435                 440                 445             


Ser Glu Thr Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln Gln Pro 
    450                 455                 460                 


Val Arg Ala Glu Asn Gln Val Asn Val Thr Cys Gln Val Arg Lys Phe 
465                 470                 475                 480 


Tyr Pro Gln Arg Leu Gln Leu Thr Trp Leu Glu Asn Gly Asn Val Ser 
                485                 490                 495     


Arg Thr Glu Thr Ala Ser Thr Val Thr Glu Asn Lys Asp Gly Thr Tyr 
            500                 505                 510         


Asn Trp Met Ser Trp Leu Leu Val Asn Val Ser Ala His Arg Asp Asp 
        515                 520                 525             


Val Lys Leu Thr Cys Gln Val Glu His Asp Gly Gln Pro Ala Val Ser 
    530                 535                 540                 


Lys Ser His Asp Leu Lys Val Ser Ala His Pro Lys Glu Gln Gly Ser 
545                 550                 555                 560 


Asn Thr Ala Ala Glu Asn Thr Gly Ser Asn Glu Arg Asn Ile Tyr Ala 
                565                 570                 575     


Ala Ala His His His His His His 
            580                 


<210>  87
<211>  573
<212>  PRT
<213>  artificial

<220>
<223>  Bicki-CD28-SIRPg (monoTGN-SIRPg) Light chain-SIRPg

<400>  87

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 His Ala Ser Gln Asn Ile Tyr Val Trp 
            20                  25                  30          


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


Tyr Lys Ala Ser Asn Leu His Thr 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 Gly Gln Thr Tyr Pro Tyr 
                85                  90                  95      


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


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


Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
    130                 135                 140                 


Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
145                 150                 155                 160 


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


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


Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 
        195                 200                 205             


Pro Lys Ser Cys Asp Lys Ala Ala Ala Gly Gly Gly Gly Ser Gly Gly 
    210                 215                 220                 


Gly Gly Ser Gly Gly Gly Gly Ser Glu Glu Glu Leu Gln Met Ile Gln 
225                 230                 235                 240 


Pro Glu Lys Leu Leu Leu Val Thr Val Gly Lys Thr Ala Thr Leu His 
                245                 250                 255     


Cys Thr Val Thr Ser Leu Leu Pro Val Gly Pro Val Leu Trp Phe Arg 
            260                 265                 270         


Gly Val Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu Gly His 
        275                 280                 285             


Phe Pro Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn Asn Met 
    290                 295                 300                 


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


Tyr Tyr Cys Val Lys Phe Arg Lys Gly Ser Pro Glu Asn Val Glu Phe 
                325                 330                 335     


Lys Ser Gly Pro Gly Thr Glu Met Ala Leu Gly Ala Lys Pro Ser Ala 
            340                 345                 350         


Pro Val Val Leu Gly Pro Ala Ala Arg Thr Thr Pro Glu His Thr Val 
        355                 360                 365             


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


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


Asp Pro Thr Gly Gln Ser Val Ala Tyr Ser Ile Arg Ser Thr Ala Arg 
                405                 410                 415     


Val Val Leu Asp Pro Trp Asp Val Arg Ser Gln Val Ile Cys Glu Val 
            420                 425                 430         


Ala His Val Thr Leu Gln Gly Asp Pro Leu Arg Gly Thr Ala Asn Leu 
        435                 440                 445             


Ser Glu Ala Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln Gln Pro 
    450                 455                 460                 


Met Arg Val Gly Asn Gln Val Asn Val Thr Cys Gln Val Arg Lys Phe 
465                 470                 475                 480 


Tyr Pro Gln Ser Leu Gln Leu Thr Trp Ser Glu Asn Gly Asn Val Cys 
                485                 490                 495     


Gln Arg Glu Thr Ala Ser Thr Leu Thr Glu Asn Lys Asp Gly Thr Tyr 
            500                 505                 510         


Asn Trp Thr Ser Trp Phe Leu Val Asn Ile Ser Asp Gln Arg Asp Asp 
        515                 520                 525             


Val Val Leu Thr Cys Gln Val Lys His Asp Gly Gln Leu Ala Val Ser 
    530                 535                 540                 


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


Asp Ala Thr Pro Ala Ala Ala His His His His His His 
                565                 570             


