                        б

<110>  Ŵҩݣ޹˾
<120>  ͿӡƱ;
<130>  P00007CN009 
<160>  31    
<170>  PatentIn汾3.3
<210>  1
<211>  132
<212>  PRT
<213>  (Camelus Linnaeus)
<220>  
<223>  PD-L1VHH
<400>  1
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Gln Ala Ser Ala Tyr Thr Ile Ser Arg Asn 
            20                  25                  30          
Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gln Arg Glu Gly Val 
        35                  40                  45              
Ala Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr Ser Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Leu Gly Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Glu Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu Ala 
            100                 105                 110         
Phe Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             
Thr Val Ser Ser 
    130         
<210>  2
<211>  132
<212>  PRT
<213>  ˹
<220>
<223>  PD-L1ԴVHH
<400>  2
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Ala Tyr Thr Ile Ser Arg Asn 
            20                  25                  30          
Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              
Ala Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr Ser Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Leu Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu Ala 
            100                 105                 110         
Phe Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly Gln Gly Thr Leu Val 
        115                 120                 125             
Thr Val Ser Ser 
    130         
<210>  3
<211>  10
<212>  PRT
<213>  (Camelus Linnaeus)
<220>  
<223>  PD-L1VH CDR1
<400>  3
Ala Tyr Thr Ile Ser Arg Asn Ser Met Gly 
1               5                   10  
<210>  4
<211>  7
<212>  PRT
<213>  (Camelus Linnaeus)
<220>  
<223>  PD-L1VH CDR2
<400>  4
Ile Glu Ser Asp Gly Ser Thr 
1               5           
<210>  5
<211>  26
<212>  PRT
<213>  (Camelus Linnaeus)
<220>  
<223>  PD-L1VH CDR3
<400>  5
Ala Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu 
1               5                   10                  15      
Ala Phe Met Thr Leu Pro Ala Leu Asn Tyr 
            20                  25      
<210>  6
<211>  355
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-110-112HC#1İ
<400>  6
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 Gln Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp His Tyr Pro Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 
            100                 105                 110         
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
        115                 120                 125             
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
    130                 135                 140                 
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
145                 150                 155                 160 
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                165                 170                 175     
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
            180                 185                 190         
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
        195                 200                 205             
Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln 
    210                 215                 220                 
Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 
225                 230                 235                 240 
Leu Arg Leu Ser Cys Ala Ala Ser Ala Tyr Thr Ile Ser Arg Asn Ser 
                245                 250                 255     
Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val Ala 
            260                 265                 270         
Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr Ser Asp Ser Val Lys Gly 
        275                 280                 285             
Arg Phe Thr Ile Ser Leu Asp Asn Ser Lys Asn Thr Leu Tyr Leu Glu 
    290                 295                 300                 
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 
305                 310                 315                 320 
Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu Ala Phe 
                325                 330                 335     
Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly Gln Gly Thr Leu Val Thr 
            340                 345                 350         
Val Ser Ser 
        355 
<210>  7
<211>  106
<212>  PRT
<213>  ˹
<220>
<223>  OX40ADI-20112VL
<400>  7
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp His Tyr Pro Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105     
<210>  8
<211>  107
<212>  PRT
<213>  ˹
<220>
<223>  ˦㶨(CL)
<400>  8
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>  9
<211>  10
<212>  PRT
<213>  ˹
<220>
<223> İ
<400>  9
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  
<210>  10
<211>  454
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-110-112HC#2İ
<400>  10
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Arg Pro Trp Tyr Ser Glu Thr Gly Thr Ser Ala Phe Asp 
            100                 105                 110         
Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 
145                 150                 155                 160 
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro 
    210                 215                 220                 
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
225                 230                 235                 240 
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                245                 250                 255     
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            260                 265                 270         
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        275                 280                 285             
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    290                 295                 300                 
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
305                 310                 315                 320 
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                325                 330                 335     
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            340                 345                 350         
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        355                 360                 365             
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    370                 375                 380                 
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
385                 390                 395                 400 
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                405                 410                 415     
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            420                 425                 430         
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        435                 440                 445             
Ser Leu Ser Pro Gly Lys 
    450                 
<210>  11
<211>  124
<212>  PRT
<213>  ˹
<220>
<223>  OX40¡ADI-20112 VH
<400>  11
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Arg Pro Trp Tyr Ser Glu Thr Gly Thr Ser Ala Phe Asp 
            100                 105                 110         
Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 
        115                 120                 
<210>  12
<211>  108
<212>  PRT
<213>  ˹
<220>
<223>  IgG1 CH1
<400>  12
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 Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            100                 105             
<210>  13
<211>  222
<212>  PRT
<213>  ˹
<220>
<223>  IgG1 Fc
<400>  13
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
145                 150                 155                 160 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
                165                 170                 175     
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
            180                 185                 190         
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         
<210>  14
<211>  355
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-113-112HC#1İ
<400>  14
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Ala Tyr Thr Ile Ser Arg Asn 
            20                  25                  30          
Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              
Ala Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr Ser Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Leu Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu Ala 
            100                 105                 110         
Phe Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly Gln Gly Thr Leu Val 
        115                 120                 125             
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile 
    130                 135                 140                 
Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg 
145                 150                 155                 160 
Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 
                165                 170                 175     
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp 
            180                 185                 190         
Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly 
        195                 200                 205             
Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp 
    210                 215                 220                 
Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp His Tyr Pro Thr Phe Gly 
225                 230                 235                 240 
Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val 
                245                 250                 255     
Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser 
            260                 265                 270         
Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln 
        275                 280                 285             
Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val 
    290                 295                 300                 
Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu 
305                 310                 315                 320 
Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu 
                325                 330                 335     
Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg 
            340                 345                 350         
Gly Glu Cys 
        355 
<210>  15
<211>  213
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-119-112LC#1İ
<400>  15
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp His Tyr Pro Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 
            100                 105                 110         
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
        115                 120                 125             
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
    130                 135                 140                 
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
145                 150                 155                 160 
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                165                 170                 175     
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
            180                 185                 190         
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
        195                 200                 205             
Asn Arg Gly Glu Cys 
    210             
<210>  16
<211>  588
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-119-112LC#2İ
<400>  16
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Arg Pro Trp Tyr Ser Glu Thr Gly Thr Ser Ala Phe Asp 
            100                 105                 110         
Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 
145                 150                 155                 160 
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro 
    210                 215                 220                 
Lys Ser Cys Asp Lys Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu 
225                 230                 235                 240 
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Ala Tyr 
                245                 250                 255     
Thr Ile Ser Arg Asn Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys 
            260                 265                 270         
Gly Leu Glu Gly Val Ala Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr 
        275                 280                 285             
Ser Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Leu Asp Asn Ser Lys 
    290                 295                 300                 
Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
305                 310                 315                 320 
Val Tyr Tyr Cys Ala Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala 
                325                 330                 335     
Leu Gly His Leu Ala Phe Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly 
            340                 345                 350         
Gln Gly Thr Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Cys Pro 
        355                 360                 365             
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
    370                 375                 380                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
385                 390                 395                 400 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                405                 410                 415     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            420                 425                 430         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        435                 440                 445             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    450                 455                 460                 
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
465                 470                 475                 480 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                485                 490                 495     
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            500                 505                 510         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        515                 520                 525             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    530                 535                 540                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
545                 550                 555                 560 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                565                 570                 575     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            580                 585             
<210>  17
<211>  596
<212>  PRT
<213>  ˹
<220>
<223>  OX40/PD-L1˫ԿBi-122-112LC#2İ
<400>  17
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Ala Tyr Thr Ile Ser Arg Asn 
            20                  25                  30          
Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              
Ala Ala Ile Glu Ser Asp Gly Ser Thr Ser Tyr Ser Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Leu Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Glu Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Pro Lys Val Gly Leu Gly Pro Arg Thr Ala Leu Gly His Leu Ala 
            100                 105                 110         
Phe Met Thr Leu Pro Ala Leu Asn Tyr Trp Gly Gln Gly Thr Leu Val 
        115                 120                 125             
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
    130                 135                 140                 
Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu 
145                 150                 155                 160 
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met 
                165                 170                 175     
His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Val 
            180                 185                 190         
Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys Gly 
        195                 200                 205             
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 
    210                 215                 220                 
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
225                 230                 235                 240 
Gly Arg Pro Trp Tyr Ser Glu Thr Gly Thr Ser Ala Phe Asp Ile Trp 
                245                 250                 255     
Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
            260                 265                 270         
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
        275                 280                 285             
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
    290                 295                 300                 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
305                 310                 315                 320 
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
                325                 330                 335     
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
            340                 345                 350         
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser 
        355                 360                 365             
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
    370                 375                 380                 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
385                 390                 395                 400 
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                405                 410                 415     
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            420                 425                 430         
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        435                 440                 445             
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    450                 455                 460                 
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
465                 470                 475                 480 
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                485                 490                 495     
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
            500                 505                 510         
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        515                 520                 525             
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    530                 535                 540                 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
545                 550                 555                 560 
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                565                 570                 575     
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            580                 585                 590         
Ser Pro Gly Lys 
        595     
<210>  18
<211>  214
<212>  PRT
<213>  ˹
<220>
<223>  VEGF/GITR˫ԿBi-2-50#1İ
<400>  18
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile 
        35                  40                  45              
Tyr Phe Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Thr Val Pro Trp 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 
<210>  19
<211>  453
<212>  PRT
<213>  ˹
<220>
<223>  VEGFAvastin 
<400>  19
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          
Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  
Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr Phe Asp Val 
            100                 105                 110         
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 
    210                 215                 220                 
Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
225                 230                 235                 240 
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                245                 250                 255     
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            260                 265                 270         
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        275                 280                 285             
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
    290                 295                 300                 
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
305                 310                 315                 320 
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                325                 330                 335     
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
            340                 345                 350         
Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
        355                 360                 365             
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    370                 375                 380                 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
385                 390                 395                 400 
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
                405                 410                 415     
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            420                 425                 430         
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        435                 440                 445             
Leu Ser Pro Gly Lys 
    450             
<210>  20
<211>  107
<212>  PRT
<213>  ˹
<220>
<223>  VEGFAvastin 
<400>  20
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      

Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile 
        35                  40                  45              
Tyr Phe Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Thr Val Pro Trp 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         
<210>  21
<211>  581
<212>  PRT
<213>  ˹
<220>
<223>  VEGF/GITR˫ԿBi-2-50#2İ
<400>  21
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          
Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  
Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr Phe Asp Val 
            100                 105                 110         
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 
    210                 215                 220                 
Ser Cys Asp Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
225                 230                 235                 240 
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
                245                 250                 255     
Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Gly Ser Ser His Met 
            260                 265                 270         
Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Thr 
        275                 280                 285             
Ile His Ser Gly Gly Gly Phe Gly Asp Tyr Ala Asn Ser Val Gln Gly 
    290                 295                 300                 
Arg Phe Thr Ile Ser Arg Asp Val Ala Lys Asn Thr Leu Tyr Leu Gln 
305                 310                 315                 320 
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Leu 
                325                 330                 335     
Ala Thr Asp Trp Arg Lys Pro Pro Gly Gln Gly Thr Gln Val Thr Val 
            340                 345                 350         
Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
        355                 360                 365             
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
    370                 375                 380                 
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
385                 390                 395                 400 
Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
                405                 410                 415     
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
            420                 425                 430         
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
        435                 440                 445             
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
    450                 455                 460                 
Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
465                 470                 475                 480 
Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
                485                 490                 495     
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
            500                 505                 510         
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
        515                 520                 525             
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
    530                 535                 540                 
Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
545                 550                 555                 560 
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
                565                 570                 575     
Leu Ser Pro Gly Lys 
            580     
<210>  22
<211>  123
<212>  PRT
<213>  ˹
<220>
<223>  VEGF¡Avastin VH
<400>  22
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          
Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  
Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr Phe Asp Val 
            100                 105                 110         
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             
<210>  23
<211>  105
<212>  PRT
<213>  ˹
<220>
<223>  IgG1 CH1
<400>  23
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 
            100                 105 
<210>  24
<211>  116
<212>  PRT
<213>  ˹
<220>
<223>  GITR VHH
<400>  24
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Gly Ser Ser 
            20                  25                  30          
His Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Thr Ile His Ser Gly Gly Gly Phe Gly Asp Tyr Ala Asn Ser Val 
    50                  55                  60                  
Gln Gly Arg Phe Thr Ile Ser Arg Asp Val Ala Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      
Ala Leu Ala Thr Asp Trp Arg Lys Pro Pro Gly Gln Gly Thr Gln Val 
            100                 105                 110         
Thr Val Ser Ser 
        115     
<210>  25
<211>  7
<212>  PRT
<213>  ˹
<220>
<223>  GITR VHH CDR1
<400>  25
Gly Phe Ala Phe Gly Ser Ser 
1               5           
<210>  26
<211>  7
<212>  PRT
<213>  ˹
<220>
<223>  GITR VHH CDR2
<400>  26
Ser Gly Gly Gly Phe Gly Asp 
1               5           
<210>  27
<211>  7
<212>  PRT
<213>  ˹
<220>
<223>  GITR VHH CDR3
<400>  27
Ala Thr Asp Trp Arg Lys Pro 
1               5           
<210>  28
<211>  571
<212>  PRT
<213>  ˹
<220>
<223>  VEGF/GITR˫ԿBi-2-51#2İ
<400>  28
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          
Gly Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  
Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr Phe Asp Val 
            100                 105                 110         
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 
    210                 215                 220                 
Ser Cys Asp Lys Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val 
225                 230                 235                 240 
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala 
                245                 250                 255     
Phe Gly Ser Ser His Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly 
            260                 265                 270         
Leu Glu Trp Val Ser Thr Ile His Ser Gly Gly Gly Phe Gly Asp Tyr 
        275                 280                 285             
Ala Asn Ser Val Gln Gly Arg Phe Thr Ile Ser Arg Asp Val Ala Lys 
    290                 295                 300                 
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
305                 310                 315                 320 
Ile Tyr Tyr Cys Ala Leu Ala Thr Asp Trp Arg Lys Pro Pro Gly Gln 
                325                 330                 335     
Gly Thr Gln Val Thr Val Ser Ser Asp Lys Thr His Thr Cys Pro Pro 
            340                 345                 350         
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
        355                 360                 365             
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
    370                 375                 380                 
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
385                 390                 395                 400 
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
                405                 410                 415     
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
            420                 425                 430         
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
        435                 440                 445             
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
    450                 455                 460                 
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
465                 470                 475                 480 
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                485                 490                 495     
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
            500                 505                 510         
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
        515                 520                 525             
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
    530                 535                 540                 
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
545                 550                 555                 560 
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570     
<210>  29
<211>  449
<212>  PRT
<213>  ˹
<220>
<223>  IgG1 (HC)
<400>  29
Glu Val Arg Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          
Ala Met Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Thr Ser Arg Asp Asp Ser Lys Asn Ala Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Gly Pro Gly Trp Tyr Ala Ala Asp Val Trp Gly Gln Gly 
            100                 105                 110         
Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    
<210>  30
<211>  214
<212>  PRT
<213>  ˹
<220>
<223>  IgG1(LC)
<400>  30
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asp Leu Pro Ala Phe 
                85                  90                  95      
Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 
<210>  31
<211>  343
<212>  PRT
<213>  ˹
<220>
<223>  GITRhcIgG-10(HC)
<400>  31
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Gly Ser Ser 
            20                  25                  30          
His Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Thr Ile His Ser Gly Gly Gly Phe Gly Asp Tyr Ala Asn Ser Val 
    50                  55                  60                  
Gln Gly Arg Phe Thr Ile Ser Arg Asp Val Ala Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      
Ala Leu Ala Thr Asp Trp Arg Lys Pro Pro Gly Gln Gly Thr Gln Val 
            100                 105                 110         
Thr Val Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
        115                 120                 125             
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
    130                 135                 140                 
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
145                 150                 155                 160 
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                165                 170                 175     
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
            180                 185                 190         
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
        195                 200                 205             
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
    210                 215                 220                 
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
225                 230                 235                 240 
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
                245                 250                 255     
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
            260                 265                 270         
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
        275                 280                 285             
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
    290                 295                 300                 
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
305                 310                 315                 320 
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                325                 330                 335     
Leu Ser Leu Ser Pro Gly Lys 
            340             

9

