﻿               ПЕРЕЧЕНЬ ПОСЛЕДОВАТЕЛЬНОСТЕЙ

<110> ЗАО «БИОКАД»

<120> ИММУНОЦИТОКИН, ВКЛЮЧАЮЩИЙ ГЕТЕРОДИМЕРНЫЙ БЕЛКОВЫЙ КОМПЛЕКС
НА ОСНОВЕ IL-15/IL-15RΑ, И ЕГО ПРИМЕНЕНИЕ

<160> 24

<170> BiSSAP 1.3.6

<210> 1
<211> 216
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15Rα-CK

<400> 1
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly Arg Thr Val 
            100                 105                 110         
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys 
        115                 120                 125             
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg 
    130                 135                 140                 
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn 
145                 150                 155                 160 
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser 
                165                 170                 175     
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys 
            180                 185                 190         
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr 
        195                 200                 205             
Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215     

<210> 2
<211> 454
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность IL15-CH1CH2CH3

<400> 2
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Ala Ser 
        115                 120                 125             
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
    130                 135                 140                 
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
145                 150                 155                 160 
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
                165                 170                 175     
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
            180                 185                 190         
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
        195                 200                 205             
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
    210                 215                 220                 
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
225                 230                 235                 240 
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            260                 265                 270         
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
        275                 280                 285             
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    290                 295                 300                 
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
305                 310                 315                 320 
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
                325                 330                 335     
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
            340                 345                 350         
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
        355                 360                 365             
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
    370                 375                 380                 
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
                405                 410                 415     
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
            420                 425                 430         
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        435                 440                 445             
Ser Leu Ser Leu Ser Pro 
    450                 

<210> 3
<211> 233
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15-CK

<400> 3
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Arg Thr 
        115                 120                 125             
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 
    130                 135                 140                 
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
145                 150                 155                 160 
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
                165                 170                 175     
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 
            180                 185                 190         
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 
        195                 200                 205             
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 
    210                 215                 220                 
Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230             

<210> 4
<211> 436
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15Rα-CH1CH2CH3

<400> 4
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly 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 Arg Val Glu 
        195                 200                 205             
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    210                 215                 220                 
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                245                 250                 255     
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            260                 265                 270         
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        275                 280                 285             
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
305                 310                 315                 320 
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                325                 330                 335     
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Asn 
            340                 345                 350         
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        355                 360                 365             
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    370                 375                 380                 
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
385                 390                 395                 400 
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                405                 410                 415     
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            420                 425                 430         
Ser Leu Ser Pro 
        435     

<210> 5
<211> 453
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15-CH1CH2CH3 knob-Fc

<400> 5
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Ala Ser 
        115                 120                 125             
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
    130                 135                 140                 
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
145                 150                 155                 160 
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
                165                 170                 175     
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
            180                 185                 190         
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
        195                 200                 205             
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
    210                 215                 220                 
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
225                 230                 235                 240 
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            260                 265                 270         
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
        275                 280                 285             
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    290                 295                 300                 
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
305                 310                 315                 320 
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
                325                 330                 335     
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
            340                 345                 350         
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Arg Asp Glu Leu Thr Lys 
        355                 360                 365             
Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
    370                 375                 380                 
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
385                 390                 395                 400 
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                405                 410                 415     
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
            420                 425                 430         
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
        435                 440                 445             
Leu Ser Leu Ser Pro 
    450             

<210> 6
<211> 436
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15Rα-CH1CH2CH3 knob-Fc

<400> 6
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly 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 Arg Val Glu 
        195                 200                 205             
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    210                 215                 220                 
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                245                 250                 255     
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            260                 265                 270         
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        275                 280                 285             
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
305                 310                 315                 320 
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                325                 330                 335     
Glu Pro Gln Val Tyr Thr Leu Pro Pro Arg Asp Glu Leu Thr Lys Asn 
            340                 345                 350         
Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        355                 360                 365             
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    370                 375                 380                 
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
385                 390                 395                 400 
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                405                 410                 415     
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            420                 425                 430         
Ser Leu Ser Pro 
        435     

<210> 7
<211> 457
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность anti-PD1 VH-CH1CH2CH3 hole-Fc

<400> 7
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Trp Met Tyr Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Ala Ile Asp Thr Gly Gly Gly Arg Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Ala Ile Ser Arg Val Asn Ala Lys Asn Thr Met 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 Asp Glu Gly Gly Gly Thr Gly Trp Gly Val Leu Lys Asp Trp 
            100                 105                 110         
Pro Tyr Gly Leu Asp Ala Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
        115                 120                 125             
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 
    130                 135                 140                 
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
145                 150                 155                 160 
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
                165                 170                 175     
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
            180                 185                 190         
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 
        195                 200                 205             
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 
    210                 215                 220                 
Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 
225                 230                 235                 240 
Cys Pro Ala Pro Glu Ala Ala 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 Asn 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 
    450                 455         

<210> 8
<211> 214
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность anti-PD1 VK-CK

<400> 8
Gln Pro Val Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln 
1               5                   10                  15      
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Ala Val 
                85                  90                  95      
Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Gln 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> 9
<211> 103
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15Rα

<400> 9
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser 
            100             

<210> 10
<211> 115
<212> PRT
<213> Природная последовательность

<223> Природная последовательность IL15

<400> 10
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser 
        115 

<210> 11
<211> 9
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность HCDR1 пролголимаба

<400> 11
Phe Thr Phe Ser Ser Tyr Trp Met Tyr 
1               5                   

<210> 12
<211> 17
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность HCDR2 пролголимаба

<400> 12
Ala Ile Asp Thr Gly Gly Gly Arg Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      
Gly 
    

<210> 13
<211> 23
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность HCDR3 пролголимаба

<400> 13
Cys Ala Arg Asp Glu Gly Gly Gly Thr Gly Trp Gly Val Leu Lys Asp 
1               5                   10                  15      
Trp Pro Tyr Gly Leu Asp Ala 
            20              

<210> 14
<211> 11
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность LCDR1 пролголимаба

<400> 14
Gly Gly Asn Asn Ile Gly Ser Lys Asn Val His 
1               5                   10      

<210> 15
<211> 7
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность LCDR2 пролголимаба

<400> 15
Arg Asp Ser Asn Arg Pro Ser 
1               5           

<210> 16
<211> 10
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность LCDR3 пролголимаба

<400> 16
Cys Gln Val Trp Asp Ser Ser Thr Ala Val 
1               5                   10  

<210> 17
<211> 129
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность VH пролголимаба

<400> 17
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Trp Met Tyr Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Ala Ile Asp Thr Gly Gly Gly Arg Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Ala Ile Ser Arg Val Asn Ala Lys Asn Thr Met 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 Asp Glu Gly Gly Gly Thr Gly Trp Gly Val Leu Lys Asp Trp 
            100                 105                 110         
Pro Tyr Gly Leu Asp Ala Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
        115                 120                 125             
Ser 
    

<210> 18
<211> 107
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность VL пролголимаба

<400> 18
Gln Pro Val Leu Thr Gln Pro Leu Ser Val Ser Val Ala Leu Gly Gln 
1               5                   10                  15      
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Thr Ala Val 
                85                  90                  95      
Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Gln 
            100                 105         

<210> 19
<211> 216
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15Rα-CK-CiA

<400> 19
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly Arg Thr Val 
            100                 105                 110         
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys 
        115                 120                 125             
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg 
    130                 135                 140                 
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn 
145                 150                 155                 160 
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser 
                165                 170                 175     
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys 
            180                 185                 190         
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr 
        195                 200                 205             
Lys Ser Phe Asn Arg Gly Glu Ala 
    210                 215     

<210> 20
<211> 454
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15-CH1CH2CH3- CiA

<400> 20
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Ala Ser 
        115                 120                 125             
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
    130                 135                 140                 
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
145                 150                 155                 160 
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
                165                 170                 175     
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
            180                 185                 190         
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
        195                 200                 205             
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
    210                 215                 220                 
Glu Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
225                 230                 235                 240 
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            260                 265                 270         
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
        275                 280                 285             
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    290                 295                 300                 
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
305                 310                 315                 320 
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
                325                 330                 335     
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
            340                 345                 350         
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
        355                 360                 365             
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
    370                 375                 380                 
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
                405                 410                 415     
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
            420                 425                 430         
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        435                 440                 445             
Ser Leu Ser Leu Ser Pro 
    450                 

<210> 21
<211> 233
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность IL15-CK- CiA

<400> 21
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Arg Thr 
        115                 120                 125             
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 
    130                 135                 140                 
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
145                 150                 155                 160 
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
                165                 170                 175     
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 
            180                 185                 190         
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 
        195                 200                 205             
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 
    210                 215                 220                 
Thr Lys Ser Phe Asn Arg Gly Glu Ala 
225                 230             

<210> 22
<211> 436
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность IL15Rα-CH1CH2CH3- CiA

<400> 22
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly 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 Arg Val Glu 
        195                 200                 205             
Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    210                 215                 220                 
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                245                 250                 255     
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            260                 265                 270         
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        275                 280                 285             
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
305                 310                 315                 320 
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                325                 330                 335     
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Asn 
            340                 345                 350         
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        355                 360                 365             
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    370                 375                 380                 
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
385                 390                 395                 400 
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                405                 410                 415     
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            420                 425                 430         
Ser Leu Ser Pro 
        435     

<210> 23
<211> 453
<212> PRT
<213> Искусственная последовательность 

<223> Искусственная последовательность IL15-CH1CH2CH3 knob-Fc

<400> 23
Asp Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
1               5                   10                  15      
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            20                  25                  30          
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        35                  40                  45              
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    50                  55                  60                  
Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn 
65                  70                  75                  80  
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                85                  90                  95      
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            100                 105                 110         
Asn Thr Ser Ala Gly Gly Lys Pro Gly Gly Ser Ala Gly Gly Ala Ser 
        115                 120                 125             
Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
    130                 135                 140                 
Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
145                 150                 155                 160 
Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
                165                 170                 175     
His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
            180                 185                 190         
Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
        195                 200                 205             
Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
    210                 215                 220                 
Glu Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
225                 230                 235                 240 
Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            260                 265                 270         
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
        275                 280                 285             
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    290                 295                 300                 
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
305                 310                 315                 320 
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
                325                 330                 335     
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
            340                 345                 350         
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Arg Asp Glu Leu Thr Lys 
        355                 360                 365             
Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
    370                 375                 380                 
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
385                 390                 395                 400 
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                405                 410                 415     
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
            420                 425                 430         
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
        435                 440                 445             
Leu Ser Leu Ser Pro 
    450             

<210> 24
<211> 436
<212> PRT
<213> Искусственная последовательность 
 
<223> Искусственная последовательность IL15Rα-CH1CH2CH3 knob-Fc

<400> 24
Asp Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      
Lys Glu Pro Ala Ala Ser Ser Gly Ala Glu Gly Gly Gly 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 Arg Val Glu 
        195                 200                 205             
Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    210                 215                 220                 
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                245                 250                 255     
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            260                 265                 270         
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        275                 280                 285             
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
305                 310                 315                 320 
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                325                 330                 335     
Glu Pro Gln Val Tyr Thr Leu Pro Pro Arg Asp Glu Leu Thr Lys Asn 
            340                 345                 350         
Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        355                 360                 365             
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    370                 375                 380                 
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
385                 390                 395                 400 
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                405                 410                 415     
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            420                 425                 430         
Ser Leu Ser Pro 
        435     

