                           

<110>  Ŵҩݣ޹˾
 
<120>  PCSK9弰;

<130>  PF 160815CNI

<160>  53    

<170>  PatentIn version 3.3

<210>  1
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  1

Gly Ser Ile Ser Ser Ser Ser Tyr Tyr Trp Gly 
1               5                   10      


<210>  2
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR2

<400>  2

Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  3
<211>  18
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR3

<400>  3

Ala Arg Glu Gly Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp Phe 
1               5                   10                  15      


Asp Pro 
        


<210>  4
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  4

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala 
1               5                   10      


<210>  5
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR2

<400>  5

Asp Ala Ser Asn Arg Ala Thr 
1               5           


<210>  6
<211>  8
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR3

<400>  6

Gln Gln Arg Arg Asn Trp Phe Thr 
1               5               


<210>  7
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  7

Gly Ser Val Ser Ser Ser Ser Tyr Tyr Trp Gly 
1               5                   10      


<210>  8
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  8

Gly Ser Ile Val Ser Ser Ser Tyr Tyr Trp Ala 
1               5                   10      


<210>  9
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  9

Gly Ser Ile Arg Ser Ser Ala Tyr Tyr Trp Gly 
1               5                   10      

<210>  10
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  10

Gly Ser Ile Ser Ser Ala Ser Tyr Tyr Trp Ser 
1               5                   10      


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

<220>
<223>  ɱCDR1

<400>  11

Gly Ser Ile Gly Ser Ser Ser Tyr Tyr Trp Ala 
1               5                   10      


<210>  12
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  12

Gly Ser Ile Gly Ser Ser Ser Tyr Tyr Trp Thr 
1               5                   10      


<210>  13
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR1

<400>  13

Gly Ser Ile Trp Ser Ser Ser Tyr Tyr Trp Thr 
1               5                   10      


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

<220>
<223>  ɱCDR2

<400>  14

Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Phe Leu Lys Ser 
1               5                   10                  15      


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

<220>
<223>  ɱCDR2

<400>  15

Ser Ala Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


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

<220>
<223>  ɱCDR2

<400>  16

Ser Ile Asn Tyr Lys Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  17
<211>  16
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR2

<400>  17

Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


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

<220>
<223>  ɱCDR3

<400>  18

Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp Phe 
1               5                   10                  15      


Asp Pro 
        


<210>  19
<211>  18
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR3

<400>  19

Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp Phe 
1               5                   10                  15      


Gly Pro 
        


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

<220>
<223>  ɱCDR1


<220>
<221>  misc_feature
<222>  (3)..(3) 
<223>  X1ѡVI

<220>
<221>  misc_feature
<222>  (4)..(4) 
<223>  X2ѡSVRGW 

<220>
<221>  misc_feature
<222>  (6)..(6) 
<223>  X3ѡSA 

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  X4ѡSA

<220>
<221>  misc_feature
<222>  (11)..(11) 
<223>  X5ѡGAST 

<400>  20

Gly Ser X1  X2 Ser X3  X4  Tyr Tyr  Trp X5 
1               5                   10      
             


<210>  21
<211>  16
<212>  PRT
<213>  ˹

<220>
<223> ɱCDR2


<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  X1ѡIA

<220>
<221>  misc_feature
<222>  (3)..(3) 
<223>  X2ѡYN 

<220>
<221>  misc_feature
<222>  (5)..(5) 
<223>  X3ѡSKR 

<220>
<221>  misc_feature
<222>  (13)..(13)
<223>  X4ѡSF 


<400>  21


Ser  X1  X2 Tyr X3 Gly Ser Thr Tyr  Tyr Asn Pro X4 Leu Lys Ser 
1               5                   10                  15      


<210>  22
<211>  18
<212>  PRT
<213>  ˹

<220>
<223>  ɱCDR3


<220>
<221>  misc_feature
<222>  (4)..(4)
<223>  X1ѡGN

<220>
<221>  misc_feature
<222>  (17)..(17)
<223>  X2ѡDG

<400>  22

Ala Arg Glu X1 Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp Phe 
1               5                   10                  15      


X2 Pro 

<210>  23
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-02396ɱ

<400>  23

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Gly Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  24
<211>  106
<212>  PRT
<213>  ˹

<220>
<223> ɱ

<400>  24

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105     


<210>  25
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09111ɱ

<400>  25

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  26
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09112ɱ

<400>  26

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Phe 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  27
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09113ɱ

<400>  27

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ala Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  28
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10085ɱ

<400>  28

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Val Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Lys Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  29
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10086ɱ

<400>  29

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Arg Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  30
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10087ɱ

<400>  30

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ala 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  31
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10088ɱ

<400>  31

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  32
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10089ɱ

<400>  32

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  33
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10090ɱ

<400>  33

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Trp Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  34
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-02396

<400>  34

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Gly Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


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

<220>
<223>  

<400>  35

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr 
            20                  25                  30          


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


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


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Arg Asn Trp Phe 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>  36
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09111

<400>  36

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  37
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09112

<400>  37

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Phe 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  38
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-09113

<400>  38

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ala Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  39
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10085

<400>  39

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Val Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Lys Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  40
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10086

<400>  40

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Arg Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  41
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10087

<400>  41

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ala 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Gly Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  42
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10088

<400>  42

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  43
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10089

<400>  43

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Gly Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  44
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  ADI-10090

<400>  44

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Trp Ser Ser 
            20                  25                  30          


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


Trp Ile Gly Ser Ile Asn Tyr Arg Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Glu Asn Ser Gly Val Val Pro Ala Ala Gly Pro Asn Trp 
            100                 105                 110         


Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr Tyr Thr 
        195                 200                 205             


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


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
225                 230                 235                 240 


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    290                 295                 300                 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


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


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


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


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


Ser Pro Gly 
    450     


<210>  45
<211>  26
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR1

<400>  45

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly 
            20                  25      


<210>  46
<211>  14
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR2

<400>  46

Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly 
1               5                   10                  


<210>  47
<211>  30
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR3

<400>  47

Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys 
1               5                   10                  15      


Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys 
            20                  25                  30  


<210>  48
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR4

<400>  48

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
1               5                   10      


<210>  49
<211>  23
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR1

<400>  49

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


Glu Arg Ala Thr Leu Ser Cys 
            20              


<210>  50
<211>  15
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR2

<400>  50

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 
1               5                   10                  15  


<210>  51
<211>  32
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR3

<400>  51

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
1               5                   10                  15      


Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys 
            20                  25                  30          


<210>  52
<211>  10
<212>  PRT
<213>  ˹

<220>
<223>  ɱFR4

<400>  52

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
1               5                   10  


<210>  53
<211>  692
<212>  PRT


<220>
<223>  PCSK9ԭİ

<400>  53

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


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


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Asp Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln 
    690         


