                         SEQUENCE LISTING

<110>  Ospedale Pediatrico Bambino Ges
 
<120>  CAR-CD30 T cells for treatment of CD30+ Tumors

<130>  PCT41700

<150>  IT102018000003464
<151>  2018-03-13

<160>  43    

<170>  PatentIn version 3.5

<210>  1
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  signal peptide

<400>  1

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys 
            


<210>  2
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AC10 VL sequence

<400>  2

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


Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Phe Asp 
            20                  25                  30          


Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Val Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile Pro Ala 
    50                  55                  60                  


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


Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ser Asn 
                85                  90                  95      


Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110     


<210>  3
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AC10 VH sequence

<400>  3

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


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


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


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


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


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


Ala Asn Tyr Gly Asn Tyr Trp Phe Ala Tyr Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ala 
        115         


<210>  4
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  trackable marker DeltaCD34

<400>  4

Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser Thr Asn Val Ser 
1               5                   10                  15      


<210>  5
<211>  272
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  trackable marker DeltaCD19

<400>  5

Pro Glu Glu Pro Leu Val Val Lys Val Glu Glu Gly Asp Asn Ala Val 
1               5                   10                  15      


Leu Gln Cys Leu Lys Gly Thr Ser Asp Gly Pro Thr Gln Gln Leu Thr 
            20                  25                  30          


Trp Ser Arg Glu Ser Pro Leu Lys Pro Phe Leu Lys Leu Ser Leu Gly 
        35                  40                  45              


Leu Pro Gly Leu Gly Ile His Met Arg Pro Leu Ala Ile Trp Leu Phe 
    50                  55                  60                  


Ile Phe Asn Val Ser Gln Gln Met Gly Gly Phe Tyr Leu Cys Gln Pro 
65                  70                  75                  80  


Gly Pro Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr Val Asn Val 
                85                  90                  95      


Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp Leu Gly Gly 
            100                 105                 110         


Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro Ser Ser Pro 
        115                 120                 125             


Ser Gly Lys Leu Met Ser Pro Lys Leu Tyr Val Trp Ala Lys Asp Arg 
    130                 135                 140                 


Pro Glu Ile Trp Glu Gly Glu Pro Pro Cys Leu Pro Pro Arg Asp Ser 
145                 150                 155                 160 


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


Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser Arg Gly Pro 
            180                 185                 190         


Leu Ser Trp Thr His Val His Pro Lys Gly Pro Lys Ser Leu Leu Ser 
        195                 200                 205             


Leu Glu Leu Lys Asp Asp Arg Pro Ala Arg Asp Met Trp Val Met Glu 
    210                 215                 220                 


Thr Gly Leu Leu Leu Pro Arg Ala Thr Ala Gln Asp Ala Gly Lys Tyr 
225                 230                 235                 240 


Tyr Cys His Arg Gly Asn Leu Thr Met Ser Phe His Leu Glu Ile Thr 
                245                 250                 255     


Ala Arg Pro Val Leu Trp His Trp Leu Leu Arg Thr Gly Gly Trp Lys 
            260                 265                 270         


<210>  6
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  trackable marker NGFR

<400>  6

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


Lys Ala Cys Asn Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn 
            20                  25                  30          


Gln Thr Val Cys Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val 
        35                  40                  45              


Val Ser Ala Thr Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu 
    50                  55                  60                  


Gln Ser Met Ser Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg 
65                  70                  75                  80  


Cys Ala Tyr Gly Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala 
                85                  90                  95      


Cys Arg Val Cys Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp 
            100                 105                 110         


Lys Gln Asn Thr Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp 
        115                 120                 125             


Glu Ala Asn His Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp 
    130                 135                 140                 


Thr Glu Arg Gln Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys 
145                 150                 155                 160 


Glu Glu Ile Pro Gly Arg Trp Ile Thr Arg Ser Thr Pro Pro Glu Gly 
                165                 170                 175     


Ser Asp Ser Thr Ala Pro Ser Thr Gln Glu Pro Glu Ala Pro Pro Glu 
            180                 185                 190         


Gln Asp Leu Ile Ala Ser Thr Val Ala Gly Val Val Thr Thr Val Met 
        195                 200                 205             


Gly Ser Ser Gln Pro Val Val Thr Arg Gly Thr Thr Asp Asn 
    210                 215                 220         


<210>  7
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge CD8alpha

<400>  7

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro 
1               5                   10                  15      


Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val 
            20                  25                  30          


His Thr Arg Gly Leu Asp Phe Ala 
        35                  40  


<210>  8
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge CD28

<400>  8

Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn 
1               5                   10                  15      


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


Phe Pro Gly Pro Ser Lys Pro 
        35                  


<210>  9
<211>  229
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge CH2CH3

<400>  9

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro Glu Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 


Leu Ser Leu Gly Lys 
225                 


<210>  10
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge CH3

<400>  10

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Gly Gln Pro Arg 
1               5                   10                  15      


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
            20                  25                  30          


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
        35                  40                  45              


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
    50                  55                  60                  


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


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
                85                  90                  95      


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
            100                 105                 110         


Leu Ser Leu Ser Leu Gly Lys 
        115                 


<210>  11
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  spacer

<400>  11

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr 
1               5                   10      


<210>  12
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge CD8alpha

<400>  12

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala 
1               5                   10                  15      


Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala 
            20                  25                  


<210>  13
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  trans membrane domain CD28TM

<400>  13

Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
1               5                   10                  15      


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 
            20                  25          


<210>  14
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  trans membrane domain CD8aTM

<400>  14

Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu 
1               5                   10                  15      


Leu Leu Ser Leu Val Ile Thr 
            20              


<210>  15
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mouse igG3 upper hinge (mIgG3UH)

<400>  15

Pro Lys Pro Ser Thr Pro Pro Gly Ser Ser 
1               5                   10  


<210>  16
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mouse igG3 upper hinge (mIgG3UH)2

<400>  16

Pro Lys Pro Ser Thr Pro Pro Gly Ser Ser Pro Lys Pro Ser Thr Pro 
1               5                   10                  15      


Pro Gly Ser Ser 
            20  


<210>  17
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G4S)2 linker

<400>  17

Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   


<210>  18
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G4S)4 linker

<400>  18

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Gly Gly Gly Ser 
            20  


<210>  19
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G4SG2 linker

<400>  19

Gly Gly Gly Gly Ser Gly Gly 
1               5           


<210>  20
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G3SG4 linker

<400>  20

Gly Gly Gly Ser Gly Gly Gly Gly 
1               5               


<210>  21
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 cytoplasmic sequence

<400>  21

Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr 
1               5                   10                  15      


Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro 
            20                  25                  30          


Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        35                  40      


<210>  22
<211>  42
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD137 (4-1BB) sequence

<400>  22

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met 
1               5                   10                  15      


Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe 
            20                  25                  30          


Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu 
        35                  40          


<210>  23
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3-Zeta chain

<400>  23

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
1               5                   10                  15      


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
            20                  25                  30          


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
        35                  40                  45              


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
    50                  55                  60                  


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
65                  70                  75                  80  


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
                85                  90                  95      


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            100                 105                 110         


<210>  24
<211>  36
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  OX40 sequence

<400>  24

Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro Pro Gly Gly Gly 
1               5                   10                  15      


Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp Ala His Ser Thr 
            20                  25                  30          


Leu Ala Lys Ile 
        35      


<210>  25
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD8a cytoplasmic

<400>  25

Leu Tyr Cys Asn His Arg Asn 
1               5           


<210>  26
<211>  542
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD30 chimeric antigen receptor molecule

<400>  26

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


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


Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln 
        35                  40                  45              


Ser Val Asp Phe Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys 
    50                  55                  60                  


Pro Gly Gln Pro Pro Lys Val Leu Ile Tyr Ala Ala Ser Asn Leu Glu 
65                  70                  75                  80  


Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
                85                  90                  95      


Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr 
            100                 105                 110         


Cys Gln Gln Ser Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


Leu Glu Ile Lys Gly Gly Gly Ser Gly Gly Gly Gly Gln Ile Gln Leu 
    130                 135                 140                 


Gln Gln Ser Gly Pro Glu Val Val Lys Pro Gly Ala Ser Val Lys Ile 
145                 150                 155                 160 


Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Tyr Ile Thr Trp 
                165                 170                 175     


Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly Trp Ile Tyr 
            180                 185                 190         


Pro Gly Ser Gly Asn Thr Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala 
        195                 200                 205             


Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Phe Met Gln Leu Ser 
    210                 215                 220                 


Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Asn Tyr Gly 
225                 230                 235                 240 


Asn Tyr Trp Phe Ala Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser 
                245                 250                 255     


Ala Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser Thr 
            260                 265                 270         


Asn Val Ser Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 
        275                 280                 285             


Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 
    290                 295                 300                 


Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile 
305                 310                 315                 320 


Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val 
                325                 330                 335     


Ile Thr Leu Tyr Cys Asn His Arg Asn Glu Phe Arg Ser Lys Arg Ser 
            340                 345                 350         


Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly 
        355                 360                 365             


Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala 
    370                 375                 380                 


Ala Tyr Arg Ser Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys 
385                 390                 395                 400 


Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys 
                405                 410                 415     


Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val 
            420                 425                 430         


Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn 
        435                 440                 445             


Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val 
    450                 455                 460                 


Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg 
465                 470                 475                 480 


Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys 
                485                 490                 495     


Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg 
            500                 505                 510         


Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys 
        515                 520                 525             


Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
    530                 535                 540         


<210>  27
<211>  536
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD30 chimeric antigen receptor molecule

<400>  27

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


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


Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln 
        35                  40                  45              


Ser Val Asp Phe Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys 
    50                  55                  60                  


Pro Gly Gln Pro Pro Lys Val Leu Ile Tyr Ala Ala Ser Asn Leu Glu 
65                  70                  75                  80  


Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
                85                  90                  95      


Thr Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr 
            100                 105                 110         


Cys Gln Gln Ser Asn Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


Leu Glu Ile Lys Gly Gly Gly Ser Gly Gly Gly Gly Gln Ile Gln Leu 
    130                 135                 140                 


Gln Gln Ser Gly Pro Glu Val Val Lys Pro Gly Ala Ser Val Lys Ile 
145                 150                 155                 160 


Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr Tyr Ile Thr Trp 
                165                 170                 175     


Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile Gly Trp Ile Tyr 
            180                 185                 190         


Pro Gly Ser Gly Asn Thr Lys Tyr Asn Glu Lys Phe Lys Gly Lys Ala 
        195                 200                 205             


Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Phe Met Gln Leu Ser 
    210                 215                 220                 


Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Phe Cys Ala Asn Tyr Gly 
225                 230                 235                 240 


Asn Tyr Trp Phe Ala Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser 
                245                 250                 255     


Ala Gly Ser Glu Leu Pro Thr Gln Gly Thr Phe Ser Asn Val Ser Thr 
            260                 265                 270         


Asn Val Ser Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 
        275                 280                 285             


Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 
    290                 295                 300                 


Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile 
305                 310                 315                 320 


Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val 
                325                 330                 335     


Ile Thr Leu Tyr Cys Asn His Arg Asn Glu Phe Arg Ser Lys Arg Ser 
            340                 345                 350         


Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly 
        355                 360                 365             


Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala 
    370                 375                 380                 


Ala Tyr Arg Ser Arg Asp Gln Arg Leu Pro Pro Asp Ala His Lys Pro 
385                 390                 395                 400 


Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu Glu Gln Ala Asp 
                405                 410                 415     


Ala His Ser Thr Leu Ala Lys Ile Arg Val Lys Phe Ser Arg Ser Ala 
            420                 425                 430         


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
        435                 440                 445             


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
    450                 455                 460                 


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
465                 470                 475                 480 


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
                485                 490                 495     


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
            500                 505                 510         


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
        515                 520                 525             


His Met Gln Ala Leu Pro Pro Arg 
    530                 535     


<210>  28
<211>  1629
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:26

<400>  28
atggagtttg ggctctcctg gctcttcctg gtcgcgattc tgaagggggt ccagtgttca       60

cgagatatcg tcctgactca gagtcctgcc agcctggcag tctccctggg acagagagct      120

accataagtt gtaaagcatc acagtctgtt gatttcgatg gcgacagcta tatgaattgg      180

taccagcaaa aacccggcca gcccccgaaa gttttgatct atgcagcctc taacttggaa      240

agcggcattc ctgcgcgatt cagtggcagc gggagtggta cagatttcac cctgaacata      300

cacccagtcg aagaggagga cgcagccaca tattactgcc aacaatctaa cgaggatcca      360

tggacttttg ggggcggcac taaactcgaa atcaagggcg gaggttcagg cggaggaggg      420

cagattcaac tgcagcaatc aggacccgag gtggtcaaac caggtgccag tgtcaagata      480

tcttgcaagg catccggata tacatttacc gactattaca ttacctgggt caagcagaaa      540

cccgggcaag gacttgaatg gattggatgg atctaccctg gtagcggcaa caccaaatac      600

aacgaaaagt ttaaagggaa ggcaaccctg actgtagaca cctccagctc cacagcattc      660

atgcagctct cctcactgac ctccgaggac acagcagtgt atttctgtgc taattacggt      720

aattactggt tcgcctattg gggccaggga acccaagtga ccgtttcagc tggatccgaa      780

cttcctactc aggggacttt ctcaaacgtt agcacaaacg taagtcccgc cccaagaccc      840

cccacacctg cgccgaccat tgcttctcaa cccctgagtt tgagacccga ggcctgccgg      900

ccagctgccg gcggggccgt gcatacaaga ggactcgatt tcgcttgcga catctacatc      960

tgggctcccc tcgctggcac ctgtggggtg ctgctgctgt cactcgtgat caccctttat     1020

tgcaaccatc gaaacgaatt cagaagtaaa cggtcaaggc ttctgcacag cgattatatg     1080

aatatgacac caagaagacc tggtccaacc cggaaacact atcagcccta cgcgccccct     1140

agagacttcg cagcataccg ctctaagaga gggagaaaaa aattgctcta tatttttaaa     1200

caaccattta tgaggcccgt acagacaact caggaagagg atggctgtag ttgccgcttc     1260

ccagaggagg aggaaggagg ctgcgagttg agagttaaat tcagtagaag tgcggatgcg     1320

cctgcttacc agcagggcca gaaccaactg tacaatgaac tgaatctcgg gcgccgagaa     1380

gagtatgacg tcctcgataa gcggaggggt agggatcctg aaatgggtgg gaagccaaga     1440

agaaaaaacc cccaggaagg actgtataac gaacttcaga aggacaagat ggcagaggcc     1500

tactctgaga ttggcatgaa aggcgaacga cggcgcggta aaggtcatga cgggctgtac     1560

cagggcctgt ccacagcgac gaaggacact tacgacgccc tgcacatgca ggcactcccc     1620

cccaggtga                                                             1629


<210>  29
<211>  63
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:1

<400>  29
atggagtttg ggctctcctg gctcttcctg gtcgcgattc tgaagggggt ccagtgttca       60

cga                                                                     63


<210>  30
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO: 2

<400>  30
gatatcgtcc tgactcagag tcctgccagc ctggcagtct ccctgggaca gagagctacc       60

ataagttgta aagcatcaca gtctgttgat ttcgatggcg acagctatat gaattggtac      120

cagcaaaaac ccggccagcc cccgaaagtt ttgatctatg cagcctctaa cttggaaagc      180

ggcattcctg cgcgattcag tggcagcggg agtggtacag atttcaccct gaacatacac      240

ccagtcgaag aggaggacgc agccacatat tactgccaac aatctaacga ggatccatgg      300

acttttgggg gcggcactaa actcgaaatc aag                                   333


<210>  31
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:20

<400>  31
ggcggaggtt caggcggagg aggg                                              24


<210>  32
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:3

<400>  32
gatatcgtcc tgactcagag tcctgccagc ctggcagtct ccctgggaca gagagctacc       60

ataagttgta aagcatcaca gtctgttgat ttcgatggcg acagctatat gaattggtac      120

cagcaaaaac ccggccagcc cccgaaagtt ttgatctatg cagcctctaa cttggaaagc      180

ggcattcctg cgcgattcag tggcagcggg agtggtacag atttcaccct gaacatacac      240

ccagtcgaag aggaggacgc agccacatat tactgccaac aatctaacga ggatccatgg      300

acttttgggg gcggcactaa actcgaaatc aag                                   333


<210>  33
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  BamH1 restriction site

<400>  33
ggatcc                                                                   6


<210>  34
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:4

<400>  34
gaacttccta ctcaggggac tttctcaaac gttagcacaa acgtaagt                    48


<210>  35
<211>  120
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:7

<400>  35
cccgccccaa gaccccccac acctgcgccg accattgctt ctcaacccct gagtttgaga       60

cccgaggcct gccggccagc tgccggcggg gccgtgcata caagaggact cgatttcgct      120


<210>  36
<211>  69
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:14

<400>  36
tgcgacatct acatctgggc tcccctcgct ggcacctgtg gggtgctgct gctgtcactc       60

gtgatcacc                                                               69


<210>  37
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:25

<400>  37
ctttattgca accatcgaaa c                                                 21


<210>  38
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  EcoR1 restriction site and connection sequence

<400>  38
gaattc                                                                   6


<210>  39
<211>  123
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:21

<400>  39
agaagtaaac ggtcaaggct tctgcacagc gattatatga atatgacacc aagaagacct       60

ggtccaaccc ggaaacacta tcagccctac gcgcccccta gagacttcgc agcataccgc      120

tct                                                                    123


<210>  40
<211>  126
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:22

<400>  40
aagagaggga gaaaaaaatt gctctatatt tttaaacaac catttatgag gcccgtacag       60

acaactcagg aagaggatgg ctgtagttgc cgcttcccag aggaggagga aggaggctgc      120

gagttg                                                                 126


<210>  41
<211>  339
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:23

<400>  41
agagttaaat tcagtagaag tgcggatgcg cctgcttacc agcagggcca gaaccaactg       60

tacaatgaac tgaatctcgg gcgccgagaa gagtatgacg tcctcgataa gcggaggggt      120

agggatcctg aaatgggtgg gaagccaaga agaaaaaacc cccaggaagg actgtataac      180

gaacttcaga aggacaagat ggcagaggcc tactctgaga ttggcatgaa aggcgaacga      240

cggcgcggta aaggtcatga cgggctgtac cagggcctgt ccacagcgac gaaggacact      300

tacgacgccc tgcacatgca ggcactcccc cccaggtga                             339


<210>  42
<211>  1611
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:27

<400>  42
atggagtttg ggctctcctg gctcttcctg gtcgcgattc tgaagggggt ccagtgttca       60

cgagatatcg tcctgactca gagtcctgcc agcctggcag tctccctggg acagagagct      120

accataagtt gtaaagcatc acagtctgtt gatttcgatg gcgacagcta tatgaattgg      180

taccagcaaa aacccggcca gcccccgaaa gttttgatct atgcagcctc taacttggaa      240

agcggcattc ctgcgcgatt cagtggcagc gggagtggta cagatttcac cctgaacata      300

cacccagtcg aagaggagga cgcagccaca tattactgcc aacaatctaa cgaggatcca      360

tggacttttg ggggcggcac taaactcgaa atcaagggcg gaggttcagg cggaggaggg      420

cagattcaac tgcagcaatc aggacccgag gtggtcaaac caggtgccag tgtcaagata      480

tcttgcaagg catccggata tacatttacc gactattaca ttacctgggt caagcagaaa      540

cccgggcaag gacttgaatg gattggatgg atctaccctg gtagcggcaa caccaaatac      600

aacgaaaagt ttaaagggaa ggcaaccctg actgtagaca cctccagctc cacagcattc      660

atgcagctct cctcactgac ctccgaggac acagcagtgt atttctgtgc taattacggt      720

aattactggt tcgcctattg gggccaggga acccaagtga ccgtttcagc tggatccgaa      780

cttcctactc aggggacttt ctcaaacgtt agcacaaacg taagtcccgc cccaagaccc      840

cccacacctg cgccgaccat tgcttctcaa cccctgagtt tgagacccga ggcctgccgg      900

ccagctgccg gcggggccgt gcatacaaga ggactcgatt tcgcttgcga catctacatc      960

tgggctcccc tcgctggcac ctgtggggtg ctgctgctgt cactcgtgat caccctttat     1020

tgcaaccatc gaaacgaatt cagaagtaaa cggtcaaggc ttctgcacag cgattatatg     1080

aatatgacac caagaagacc tggtccaacc cggaaacact atcagcccta cgcgccccct     1140

agagacttcg cagcataccg ctctcgcgat caaagactcc cgcccgatgc ccacaaaccc     1200

cctggcgggg gcagctttag gacacccatt caagaagagc aggcagacgc ccacagcacc     1260

ttggccaaaa ttagagttaa attcagtaga agtgcggatg cgcctgctta ccagcagggc     1320

cagaaccaac tgtacaatga actgaatctc gggcgccgag aagagtatga cgtcctcgat     1380

aagcggaggg gtagggatcc tgaaatgggt gggaagccaa gaagaaaaaa cccccaggaa     1440

ggactgtata acgaacttca gaaggacaag atggcagagg cctactctga gattggcatg     1500

aaaggcgaac gacggcgcgg taaaggtcat gacgggctgt accagggcct gtccacagcg     1560

acgaaggaca cttacgacgc cctgcacatg caggcactcc cccccaggtg a              1611


<210>  43
<211>  108
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleotide sequence encoding SEQ ID NO:24

<400>  43
cgcgatcaaa gactcccgcc cgatgcccac aaaccccctg gcgggggcag ctttaggaca       60

cccattcaag aagagcaggc agacgcccac agcaccttgg ccaaaatt                   108


