                         б

<110>  ͲҽҩϺι˾
 
<120>  CTLA-4Ŀ弰;

<130>  C22W1531

<150>  CN202110429291.6
<151>  2021-04-21

<160>  40    

<170>  PatentIn 汾 3.5

<210>  1
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  1

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  2
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  2

Gly Phe Asn Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  3
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  3

Gly Phe Asn Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  4
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  4

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  5
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  5

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  6
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  6

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  7
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  7

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


<210>  8
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR1

<400>  8

Gly Phe Thr Val Ser Lys Asn Tyr Met Ser 
1               5                   10  


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

<220>
<223>  VH CDR2

<400>  9

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


<210>  10
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  10

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


<210>  11
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  11

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


<210>  12
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  12

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


<210>  13
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  13

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


<210>  14
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  14

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


<210>  15
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  15

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


<210>  16
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR2

<400>  16

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


<210>  17
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  17

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  18
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  18

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  19
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  19

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  20
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  20

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  21
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  21

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  22
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  22

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  23
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  23

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  24
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  VH CDR3

<400>  24

Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
1               5                   10      


<210>  25
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  25

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  26
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  26

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Asn Val Ser Lys Asn 
            20                  25                  30          


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


Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  27
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  27

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Asn Val Ser Lys Asn 
            20                  25                  30          


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


Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  28
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  28

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  29
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  29

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  30
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  30

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  31
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  31

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  32
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  VH

<400>  32

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


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Val Ser Lys Asn 
            20                  25                  30          


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


Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


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


Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  33
<211>  371
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  33

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile 
            20                  25                  30          


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr 
        35                  40                  45              


Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
    50                  55                  60                  


Leu Glu Trp Val Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
        115                 120                 125             


Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser Cys 
    130                 135                 140                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
145                 150                 155                 160 


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


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            180                 185                 190         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        195                 200                 205             


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


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
225                 230                 235                 240 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Glu 
                245                 250                 255     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            260                 265                 270         


Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
        275                 280                 285             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    290                 295                 300                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
305                 310                 315                 320 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                325                 330                 335     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            340                 345                 350         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        355                 360                 365             


Pro Gly Lys 
    370     


<210>  34
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  34

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Ala Glu Thr Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Asn Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Val Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Ile Leu Ser Arg Asp Asn Ser Asp 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  35
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  35

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Ala Glu Thr Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Asn Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Val Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Ile Leu Ser Arg Asp Asn Ser Asp 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Glu Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  36
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  36

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Ala Glu Thr Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Thr Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Val Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Ile Leu Ser Arg Asp Asn Ser Asp 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  37
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  37

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Thr Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  38
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  38

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Ala Glu Thr Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Thr Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Val Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ala Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Ile Leu Ser Arg Asp Asn Ser Asp 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Glu Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  39
<211>  372
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  39

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            20                  25                  30          


Ile Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe 
        35                  40                  45              


Thr Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys 
    50                  55                  60                  


Gly Leu Glu Trp Val Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr 
65                  70                  75                  80  


Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
                85                  90                  95      


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp 
        115                 120                 125             


Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser 
    130                 135                 140                 


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
145                 150                 155                 160 


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


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            180                 185                 190         


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        195                 200                 205             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    210                 215                 220                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
225                 230                 235                 240 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                245                 250                 255     


Glu Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            260                 265                 270         


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
        275                 280                 285             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    290                 295                 300                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
305                 310                 315                 320 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            340                 345                 350         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        355                 360                 365             


Ser Pro Gly Lys 
    370         


<210>  40
<211>  371
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  40

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile 
            20                  25                  30          


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr 
        35                  40                  45              


Val Ser Lys Asn Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
    50                  55                  60                  


Leu Glu Trp Val Ser Val Val Tyr Ser Gly Gly Ser Lys Thr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Ala Val Pro His Ser Pro Ser Ser Phe Asp Ile 
        115                 120                 125             


Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Pro Lys Ser Cys 
    130                 135                 140                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
145                 150                 155                 160 


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


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            180                 185                 190         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        195                 200                 205             


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


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
225                 230                 235                 240 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                245                 250                 255     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            260                 265                 270         


Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
        275                 280                 285             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    290                 295                 300                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
305                 310                 315                 320 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                325                 330                 335     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            340                 345                 350         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        355                 360                 365             


Pro Gly Lys 
    370     


