               SEQUENCE LISTING

<110> Indian Institute of Technology Bombay

<120> NOVEL HUMANIZED ANTI-CD19-41BB CHIMERIC ANTIGEN RECEPTOR AND ITS PREPARATION

<130> 548-2018

<150> IN201821005458
<151> 2018-02-13

<160> 57

<170> BiSSAP 1.3.6

<210> 1
<211> 119
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain heavy chain variable region

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

<210> 2
<211> 119
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain heavy chain variable region

<400> 2
Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Val Ser Leu Pro Asp Tyr 
            20                  25                  30          
Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu 
        35                  40                  45              
Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys 
    50                  55                  60                  
Ser Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys 
65                  70                  75                  80  
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
                85                  90                  95      
His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Thr Val Thr Val Ser Ser 
        115                 

<210> 3
<211> 107
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain light chain variable region

<400> 3
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210> 4
<211> 25
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 1

<400> 4
Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Ala Val Ser 
            20                  25  

<210> 5
<211> 25
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 1

<400> 5
Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu Leu Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Ala Val Tyr 
            20                  25  

<210> 6
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR CDR 1

<400> 6
Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 
1               5                   10  

<210> 7
<211> 14
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 2

<400> 7
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu Gly 
1               5                   10                  

<210> 8
<211> 16
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HC CDR2

<400> 8
Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser 
1               5                   10                  15      



<210> 9
<211> 31
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 3

<400> 9
Val Thr Ile Ile Lys Asp Thr Ser Lys Asn Gln Phe Phe Leu Lys Leu 
1               5                   10                  15      
Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
            20                  25                  30      

<210> 10
<211> 31
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 3

<400> 10
Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu 
1               5                   10                  15      
Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
            20                  25                  30      

<210> 11
<211> 12
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HC CDR3

<400> 11
His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 
1               5                   10          

<210> 12
<211> 11
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain HCVR framework region 4

<400> 12
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
1               5                   10      

<210> 13
<211> 23
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LCVR framework region 1

<400> 13
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys 
            20              

<210> 14
<211> 11
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LC CDR1

<400> 14
Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn 
1               5                   10      

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


<220> 
<223> Humanized anti-CD19 binding domain LCVR framework region 2

<400> 15
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 
1               5                   10                  15  

<210> 16
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LC CDR2

<400> 16
His Thr Ser Arg Leu His Ser Gly 
1               5               

<210> 17
<211> 31
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LCVR framework region 3

<400> 17
Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe 
1               5                   10                  15      
Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys 
            20                  25                  30      

<210> 18
<211> 9
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LC CDR3

<400> 18
Gln Gln Gly Asn Thr Asn Pro Tyr Thr 
1               5                   

<210> 19
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain LCVR framework region 4

<400> 19
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
1               5                   10  

<210> 20
<211> 15
<212> PRT
<213> Artificial Sequence


<220> 
<223> VH-VL linker sequence

<400> 20
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  

<210> 21
<211> 24
<212> PRT
<213> Artificial Sequence


<220> 
<223> CD8 alpha transmembrane domain

<400> 21
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 
1               5                   10                  15      
Ser Leu Val Ile Thr Leu Tyr Cys 
            20                  

<210> 22
<211> 44
<212> PRT
<213> Artificial Sequence


<220> 
<223> CD8 alpha hinge region

<400> 22
Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala 
1               5                   10                  15      
Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly 
            20                  25                  30          
Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
        35                  40                  45

<210> 23
<211> 42
<212> PRT
<213> Artificial Sequence


<220> 
<223> 4-1BB costimulatory domain

<400> 23
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> 24
<211> 112
<212> PRT
<213> Artificial Sequence


<220> 
<223> CD3 zeta signaling domain

<400> 24
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> 25
<211> 485
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR amino acid sequence

<400> 25
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      
His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu 
            20                  25                  30          
Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Val 
        35                  40                  45              
Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys 
    50                  55                  60                  
Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr 
65                  70                  75                  80  
Ser Ser Ser Leu Lys Ser Val Thr Ile Ile Lys Asp Thr Ser Lys Asn 
                85                  90                  95      
Gln Phe Phe Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val 
            100                 105                 110         
Tyr Tyr Cys Ala Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp 
        115                 120                 125             
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 
    130                 135                 140                 
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 
145                 150                 155                 160 
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
                165                 170                 175     
Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln 
            180                 185                 190         
Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg 
        195                 200                 205             
Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
    210                 215                 220                 
Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr 
225                 230                 235                 240 
Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly 
                245                 250                 255     
Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr 
            260                 265                 270         
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala 
        275                 280                 285             
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe 
    290                 295                 300                 
Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val 
305                 310                 315                 320 
Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys 
                325                 330                 335     
Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
            340                 345                 350         
Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
        355                 360                 365             
Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro 
    370                 375                 380                 
Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly 
385                 390                 395                 400 
Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro 
                405                 410                 415     
Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr 
            420                 425                 430         
Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly 
        435                 440                 445             
Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln 
    450                 455                 460                 
Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln 
465                 470                 475                 480 
Ala Leu Pro Pro Arg 
                485 

<210> 26
<211> 1398
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR nucleotide sequence

<400> 26
atggccctgc ctgtgacagc tctgctgctg cctcttgctc tgcttctgca tgctgctaga      60

cctcaggttc agctgcagca atggggagcc ggactgctga agccttctga gacactgtct     120

ctgacctgtg ccgtcagcgg agtgtctctg cctgattacg gcgtgtcctg gatcagacag     180

cctcctggca aaggactgga atggctggga gtgatctggg gcagcgagac aacctactac     240

agcagcagcc tgaagtccgt gaccatcatc aaggacacca gcaagaacca gttctactac     300

tacggcggca gctacgccat ggattattgg ggccagggca ccacagtgac agtttctagc     360

ggaggcggag gaagtggtgg cggaggttct ggcggcggag gatctgatat ccagatgaca     420

cagagcccta gcagcctgtc tgcctctgtg ggcgatagag tgaccattac ctgcagagcc     480

agccaggaca tctccaagta cctgaactgg tatcagcaga agcccggcaa ggcccctaag     540

ctgctgatct accacacaag cagactgcac agcggcgtgc caagcagatt ttctggcagc     600

ggctctggca ccgacttcac cttcaccatt tctagcctgc agcctgagga tatcgccacc     660

tactattgcc agcagggcaa caccctgcct tacacctttg gcggaggcac caaggtggaa     720

atcaagacca ccacaccagc tcctcggcct ccaactcctg ctcctacaat tgcctctcag     780

cctctgagcc tgaggcctga agcttgtaga cctgctgctg gcggagccgt gcataccaga     840

ggactggatt tcgcctgcga catctacatt tgggcccctc tggctggaac atgtggcgtg     900

ctgctgctct ccctggtcat caccctgtac tgcaagcggg gcagaaagaa gctgctgtac     960

atcttcaagc agcccttcat gcggcccgtg cagacaacac aagaggaaga tggctgctcc    1020

tgcagattcc ccgaggaaga agaaggcggc tgcgagctga gagtgaagtt ctccagatct    1080

gccgacgctc ctgcctatca gcagggccag aatcagctgt acaacgagct gaatctgggg    1140

cgcagagaag agtacgacgt gctggacaag agaaggggca gagatcctga gatgggcggc    1200

aagcccagac ggaagaatcc tcaagagggc ctgtataatg agctgcagaa agacaagatg    1260

gccgaggcct acagcgagat cggaatgaag ggcgaacgca gaagaggcaa gggccacgat    1320

ggactgtatc agggcctgag cacagccacc aaggatacct atgatgccct gcacatgcag    1380

gccctgccac ctagataa                                                  1398


<210> 27
<211> 485
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR amino acid sequence

<400> 27
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      
His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu 
            20                  25                  30          
Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Val 
        35                  40                  45              
Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys 
    50                  55                  60                  
Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr 
65                  70                  75                  80  
Ser Ser Ser Leu Lys Ser Val Thr Ile Ser Val Asp Thr Ser Lys Asn 
                85                  90                  95      
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val 
            100                 105                 110         
Tyr Tyr Cys Ala Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp 
        115                 120                 125             
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 
    130                 135                 140                 
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 
145                 150                 155                 160 
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
                165                 170                 175     
Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln 
            180                 185                 190         
Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg 
        195                 200                 205             
Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
    210                 215                 220                 
Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr 
225                 230                 235                 240 
Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly 
                245                 250                 255     
Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr 
            260                 265                 270         
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala 
        275                 280                 285             
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe 
    290                 295                 300                 
Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val 
305                 310                 315                 320 
Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys 
                325                 330                 335     
Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr 
            340                 345                 350         
Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu 
        355                 360                 365             
Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro 
    370                 375                 380                 
Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly 
385                 390                 395                 400 
Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro 
                405                 410                 415     
Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr 
            420                 425                 430         
Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly 
        435                 440                 445             
Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln 
    450                 455                 460                 
Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln 
465                 470                 475                 480 
Ala Leu Pro Pro Arg 
                485 

<210> 28
<211> 1461
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR nucleotide sequence

<400> 28
atggccctgc ctgtgacagc tctgctgctg cctcttgctc tgcttctgca tgccgccaga      60

cctgaagtga agctgcaaga gtctggacct ggactggtgg ccccttctca gtctctgtct     120

gtgacctgta ccgtcagcgg agtgtctctg cctgattacg gcgtgtcctg gatcagacag     180

cctcctagaa aaggcctgga atggctgggc gtgatctggg gcagcgagac aacctactac     240

aacagcgccc tgaagtcccg gctgaccatc atcaaggaca acagcaagag ccaggtgttc     300

ctgaagatga acagcctgca gaccgacgac accgccatct actactgcgc caagcactac     360

tactacggcg gcagctacgc catggattat tggggccagg gcaccagcgt gacagtttct     420

tctggtggcg gaggatctgg cggaggtgga agcggcggag gcggatctga tatccagatg     480

acccagacca caagcagcct gtctgcctct ctgggcgata gagtgaccat cagctgtaga     540

gccagccagg acatctccaa gtacctgaac tggtatcagc agaaacccga cggcaccgtg     600

aaactgctga tctaccacac cagcagactg cactctggcg tgccaagcag attttctggc     660

agcggctctg gcaccgacta cagcctgaca atcagcaacc tggaacaaga ggatatcgct     720

acctacttct gccagcaagg caacaccctg ccttacacct ttggcggagg caccaagctg     780

gaaatcacca ccacaacacc cgctcctaga ccacctacac cagctcctac aatcgccagc     840

cagcctctgt ctctgaggcc tgaagcttgt agacctgctg ctggcggagc cgtgcatacc     900

agaggactgg atttcgcctg cgacatctac atttgggccc ctctggctgg aacatgtggc     960

gtgctgctgc tgagcctggt catcaccctg tattgcaagc ggggcagaaa gaagctgctc    1020

tacatcttca agcagccctt catgcggccc gtgcagacca cacaagagga agatggctgc    1080

tcctgcagat tccccgagga agaagaaggc ggctgcgagc tgagagtgaa gttctccaga    1140

tctgccgacg ctcctgccta ccagcaggga cagaaccagc tgtacaacga gctgaacctg    1200

gggagaagag aagagtacga cgtgctggat aagcggagag gcagggaccc tgagatgggc    1260

ggaaagccta gacggaagaa tccccaagag ggcctgtata atgagctgca gaaagacaag    1320

atggccgagg cctacagcga gatcggaatg aagggcgagc gcagaagagg caagggccac    1380

gatggactgt atcagggcct gagcacagcc accaaggata cctatgatgc cctgcacatg    1440

caggccctgc cacctagata a                                              1461


<210> 29
<211> 27
<212> PRT
<213> Artificial Sequence


<220> 
<223> 4-1BB transmembrane domain

<400> 29
Ile Ile Ser Phe Phe Leu Ala Leu Thr Ser Thr Ala Leu Leu Phe Leu 
1               5                   10                  15      
Leu Phe Phe Leu Thr Leu Arg Phe Ser Val Val 
            20                  25          

<210> 30
<211> 21
<212> PRT
<213> Artificial Sequence


<220> 
<223> CD8 alpha leader sequence

<400> 30
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      
His Ala Ala Arg Pro 
            20      

<210> 31
<211> 62
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD8 alpha leader sequence

<400> 31
atggccctgc ctgtgacagc cctgctgctg cctctggctc tgctgctgca tgccgctaga     60

cc                                                                    62


<210> 32
<211> 1184
<212> DNA
<213> Artificial Sequence


<220> 
<223> EF-1 alpha promoter sequence

<400> 32
cgtgaggctc cggtgcccgt cagtgggcag agcgcacatc gcccacagtc cccgagaagt      60

tggggggagg ggtcggcaat tgaaccggtg cctagagaag gtggcgcggg gtaaactggg     120

aaagtgatgt cgtgtactgg ctccgccttt ttcccgaggg tgggggagaa ccgtatataa     180

gtgcagtagt cgccgtgaac gttctttttc gcaacgggtt tgccgccaga acacaggtaa     240

gtgccgtgtg tggttcccgc gggcctggcc tctttacggg ttatggccct tgcgtgcctt     300

gaattacttc cacctggctg cagtacgtga ttcttgatcc cgagcttcgg gttggaagtg     360

ggtgggagag ttcgaggcct tgcgcttaag gagccccttc gcctcgtgct tgagttgagg     420

cctggcctgg gcgctggggc cgccgcgtgc gaatctggtg gcaccttcgc gcctgtctcg     480

ctgctttcga taagtctcta gccatttaaa atttttgatg acctgctgcg acgctttttt     540

tctggcaaga tagtcttgta aatgcgggcc aagatctgca cactggtatt tcggtttttg     600

gggccgcggg cggcgacggg gcccgtgcgt cccagcgcac atgttcggcg aggcggggcc     660

tgcgagcgcg gccaccgaga atcggacggg ggtagtctca agctggccgg cctgctctgg     720

tgcctggcct cgcgccgccg tgtatcgccc cgccctgggc ggcaaggctg gcccggtcgg     780

caccagttgc gtgagcggaa agatggccgc ttcccggccc tgctgcaggg agctcaaaat     840

ggaggacgcg gcgctcggga gagcgggcgg gtgagtcacc cacacaaagg aaaagggcct     900

ttccgtcctc agccgtcgct tcatgtgact ccacggagta ccgggcgccg tccaggcacc     960

tcgattagtt ctcgagcttt tggagtacgt cgtctttagg ttggggggag gggttttatg    1020

cgatggagtt tccccacact gagtgggtgg agactgaagt taggccagct tggcacttga    1080

tgtaattctc cttggaattt gccctttttg agtttggatc ttggttcatt ctcaagcctc    1140

agacagtggt tcaaagtttt tttcttccat ttcaggtgtc gtga                     1184


<210> 33
<211> 488
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR amino acid sequence

<400> 33
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      
His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu 
            20                  25                  30          
Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Val 
        35                  40                  45              
Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys 
    50                  55                  60                  
Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr 
65                  70                  75                  80  
Ser Ser Ser Leu Lys Ser Val Thr Ile Ile Lys Asp Thr Ser Lys Asn 
                85                  90                  95      
Gln Phe Phe Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val 
            100                 105                 110         
Tyr Tyr Cys Ala Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp 
        115                 120                 125             
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 
    130                 135                 140                 
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 
145                 150                 155                 160 
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
                165                 170                 175     
Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln 
            180                 185                 190         
Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg 
        195                 200                 205             
Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
    210                 215                 220                 
Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr 
225                 230                 235                 240 
Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly 
                245                 250                 255     
Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr 
            260                 265                 270         
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala 
        275                 280                 285             
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe 
    290                 295                 300                 
Ala Cys Asp Ile Ile Ser Phe Phe Leu Ala Leu Thr Ser Thr Ala Leu 
305                 310                 315                 320 
Leu Phe Leu Leu Phe Phe Leu Thr Leu Arg Phe Ser Val Val Lys Arg 
                325                 330                 335     
Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro 
            340                 345                 350         
Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu 
        355                 360                 365             
Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala 
    370                 375                 380                 
Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
385                 390                 395                 400 
Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
                405                 410                 415     
Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
            420                 425                 430         
Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
        435                 440                 445             
Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
    450                 455                 460                 
Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
465                 470                 475                 480 
His Met Gln Ala Leu Pro Pro Arg 
                485             

<210> 34
<211> 1485
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR nucleotide sequence

<400> 34
ggatccgcca ccatggcatt gcctgttaca gctctgctgc tgcctctggc tctgcttctg      60

catgctgcta gacctcaggt tcagctgcag caatggggag ccggactgct gaagccttct     120

gagacactgt ctctgacctg tgccgtcagc ggagtgtctc tgcctgatta cggcgtgtcc     180

tggatcagac agcctcctgg caaaggactg gaatggctgg gagtgatctg gggcagcgag     240

acaacctact acagcagcag cctgaagtcc gtgaccatca tcaaggacac cagcaagaac     300

cagttcttcc tgaagctgag cagcgtgaca gccgccgata cagccgtgta ctactgcgcc     360

agacactact actacggcgg cagctacgcc atggattatt ggggccaggg caccacagtg     420

acagtttcta gcggaggcgg aggaagtggc ggcggaggat ctggcggtgg tggttctgat     480

atccagatga cacagagccc tagcagcctg tctgcctctg tgggcgatag agtgaccatt     540

acctgtcggg ccagccagga catctccaag tacctgaact ggtatcagca gaagcccggc     600

aaggccccta agctgctgat ctaccacaca agcagactgc acagcggcgt gccaagcaga     660

ttttctggca gcggctctgg caccgacttc accttcacca tttctagcct gcagcctgag     720

gatatcgcca cctactattg ccagcagggc aacaccctgc cttacacctt tggcggaggc     780

accaaggtgg aaatcaagac caccacacca gctcctcggc ctccaactcc tgctcctaca     840

attgcctctc agcctctgag cctgaggcct gaagcttgta gacctgctgc tggcggagcc     900

gtgcatacca gaggactgga tttcgcctgc gacatcatct cattctttct ggccctgacc     960

agcacagccc tgctgtttct gctgttcttt ctgacactgc ggttcagcgt ggtcaagcgg    1020

ggaagaaaga agctgctgta catcttcaag cagcccttca tgcggcccgt gcagacaaca    1080

caagaggaag atggctgctc ctgcagattc cccgaggaag aagaaggcgg ctgcgagctg    1140

agagtgaagt tctctagatc tgccgacgct cccgcctacc agcagggaca gaatcagctg    1200

tacaacgagc tgaatctggg gcgcagagaa gagtacgacg tgctggataa gagaagaggc    1260

agagatcccg agatgggcgg caagcctcgg agaaagaatc ctcaagaggg cctctacaat    1320

gagctgcaga aagacaagat ggccgaggcc tacagcgaga tcggaatgaa gggcgaacgc    1380

agaagaggaa agggccacga cggactgtat cagggcctga gcacagccac caaggatacc    1440

tatgatgccc tgcacatgca ggccctgcct ccaagatgaa tcgat                    1485


<210> 35
<211> 297
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain heavy chain variable region
      nucleotide sequence

<400> 35
caggttcagc tgcagcaatg gggagccgga ctgctgaagc cttctgagac actgtctctg     60

acctgtgccg tcagcggagt gtctctgcct gattacggcg tgtcctggat cagacagcct    120

cctggcaaag gactggaatg gctgggagtg atctggggca gcgagacaac ctactacagc    180

agcagcctga agtccgtgac catcatcaag gacaccagca agaaccagtt ctactactac    240

ggcggcagct acgccatgga ttattggggc cagggcacca cagtgacagt ttctagc       297


<210> 36
<211> 357
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain heavy chain variable region
      nucleotide sequence

<400> 36
caggttcagc tgcagcaatg gggagccgga ctgctgaagc cttctgagac actgtctctg      60

acctgtgccg tgtatggcgt gtccctgcct gattacggcg tgtcctggat tagacagcct     120

cctggcaaag gcctggaatg gctgggagtg atctggggca gcgagacaac ctactacagc     180

agcagcctga agtccgtgac catcagcgtg gacaccagca agaaccagtt ctccctgaag     240

ctgtctagcg tgacagccgc cgataccgcc gtgtactact gtgccagaca ctactactac     300

ggcggcagct acgccatgga ttattggggc cagggcacca cagtgacagt ttctagc        357


<210> 37
<211> 321
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain light chain variable region
      nucleotide sequence

<400> 37
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc      60

attacctgca gagccagcca ggacatctcc aagtacctga actggtatca gcagaagccc     120

ggcaaggccc ctaagctgct gatctaccac acaagcagac tgcacagcgg cgtgccaagc     180

agattttctg gcagcggctc tggcaccgac ttcaccttca ccatttctag cctgcagcct     240

gaggatatcg ccacctacta ttgccagcag ggcaacaccc tgccttacac ctttggcgga     300

ggcaccaagg tggaaatcaa g                                               321


<210> 38
<211> 135
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD8 alpha hinge region nucleotide sequence

<400> 38
accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg     60

tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg    120

gacttcgcct gtgat                                                     135


<210> 39
<211> 72
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD8 alpha transmembrane domain nucleotide sequence

<400> 39
atctacatct gggcgccctt ggccgggact tgtggggtcc ttctcctgtc actggttatc     60

accctttact gc                                                         72


<210> 40
<211> 81
<212> DNA
<213> Artificial Sequence


<220> 
<223> 4-1BB transmembrane domain nucleotide sequence

<400> 40
atcatctcat tctttctggc cctgaccagc acagccctgc tgtttctgct gttctttctg     60

acactgcggt tcagcgtggt c                                               81


<210> 41
<211> 126
<212> DNA
<213> Artificial Sequence


<220> 
<223> 4-1BB costimulatory domain nucleotide sequence

<400> 41
aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa     60

actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt    120

gaactg                                                               126


<210> 42
<211> 336
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD3 zeta signaling domain nucleotide sequence

<400> 42
agagtgaagt tcagcaggag cgcagacgcc cccgcgtacc agcagggcca gaaccagctc      60

tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc     120

cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat     180

gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc     240

cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc     300

tacgacgccc ttcacatgca ggccctgccc cctcgc                               336


<210> 43
<211> 45
<212> DNA
<213> Artificial Sequence


<220> 
<223> VH-VL linker nucleotide sequence

<400> 43
ggaggcggag gaagtggtgg cggaggttct ggcggcggag gatct                     45


<210> 44
<211> 63
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD8 alpha leader sequence

<400> 44
atggcattgc ctgttacagc tctgctgctg cctctggctc tgcttctgca tgctgctaga     60

cct                                                                   63


<210> 45
<211> 72
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD8 alpha transmembrane domain nucleotide sequence

<400> 45
atctacattt gggcccctct ggctggaaca tgtggcgtgc tgctgctcag cctggtcatc     60

accctgtact gc                                                         72


<210> 46
<211> 45
<212> DNA
<213> Artificial Sequence


<220> 
<223> VH-VL linker nucleotide sequence

<400> 46
ggaggcggag gaagtggcgg cggaggatct ggcggtggtg gttct                     45


<210> 47
<211> 126
<212> DNA
<213> Artificial Sequence


<220> 
<223> 4-1BB costimulatory domain nucleotide sequence

<400> 47
aagcggggaa gaaagaagct gctgtacatc ttcaagcagc ccttcatgcg gcccgtgcag     60

acaacacaag aggaagatgg ctgctcctgc agattccccg aggaagaaga aggcggctgc    120

gagctg                                                               126


<210> 48
<211> 339
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD3 zeta signaling domain nucloetide sequence

<400> 48
agagtgaagt tctccagatc tgccgacgct cctgcttatc agcagggcca gaaccagctg      60

tacaacgagc tgaatctggg gagaagagaa gagtacgacg tgctggataa gcggagaggc     120

agagatcctg agatgggcgg caagcccaga cggaagaatc ctcaagaggg cctgtataat     180

gagctgcaga aagacaagat ggccgaggcc tacagcgaga tcggaatgaa gggcgagcgc     240

agaagaggca aaggacacga tggactgtac cagggcctga gcacagccac caaggatacc     300

tatgatgccc tgcacatgca ggccctgcca cctagataa                            339


<210> 49
<211> 255
<212> DNA
<213> Artificial Sequence


<220> 
<223> CD3 zeta signaling domain nucleotide sequence

<400> 49
agagtgaagt tctccagatc tgccgacgct cctgcctatc agcagggcca gaatcagctg     60

tacaacgagc tgaatctggg gcgcagagaa gagtacgacg tgctggacaa gagaaggggc    120

agagatcctg agatgggcgg caagcccaga cggaagaatc ctcaagaggg cctgtataat    180

gagctgcaga aagacagagt gaagttctct agatctgccg acgctcccgc ctaccagcag    240

ggacagaatc agctg                                                     255


<210> 50
<211> 321
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain light chain variable region
      nucleotide sequence

<400> 50
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc      60

attacctgca gagccagcca ggacatcagc aagtacctga actggtatca gcagaagccc     120

ggcaaggccc ctaagctgct gatctaccac acaagcagac tgcacagcgg cgtgccaagc     180

agattttctg gcagcggctc tggcaccgac ttcaccttca ccatttctag cctgcagcct     240

gaggatatcg ccacctacta ttgccagcag ggcaacaccc tgccttacac ctttggcgga     300

ggcaccaagg tggaaatcaa g                                               321


<210> 51
<211> 321
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 binding domain light chain variable region
      nucleotide sequence

<400> 51
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc      60

attacctgtc gggccagcca ggacatctcc aagtacctga actggtatca gcagaagccc     120

ggcaaggccc ctaagctgct gatctaccac acaagcagac tgcacagcgg cgtgccaagc     180

agattttctg gcagcggctc tggcaccgac ttcaccttca ccatttctag cctgcagcct     240

gaggatatcg ccacctacta ttgccagcag ggcaacaccc tgccttacac ctttggcgga     300

ggcaccaagg tggaaatcaa g                                               321


<210> 52
<211> 488
<212> PRT
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR amino acid sequence

<400> 52
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      
His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Trp Gly Ala Gly Leu 
            20                  25                  30          
Leu Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Tyr Gly Val 
        35                  40                  45              
Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys 
    50                  55                  60                  
Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr 
65                  70                  75                  80  
Ser Ser Ser Leu Lys Ser Val Thr Ile Ser Val Asp Thr Ser Lys Asn 
                85                  90                  95      
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val 
            100                 105                 110         
Tyr Tyr Cys Ala Arg His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp 
        115                 120                 125             
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 
    130                 135                 140                 
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr 
145                 150                 155                 160 
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
                165                 170                 175     
Thr Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln 
            180                 185                 190         
Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr His Thr Ser Arg 
        195                 200                 205             
Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
    210                 215                 220                 
Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr 
225                 230                 235                 240 
Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly 
                245                 250                 255     
Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr 
            260                 265                 270         
Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala 
        275                 280                 285             
Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe 
    290                 295                 300                 
Ala Cys Asp Ile Ile Ser Phe Phe Leu Ala Leu Thr Ser Thr Ala Leu 
305                 310                 315                 320 
Leu Phe Leu Leu Phe Phe Leu Thr Leu Arg Phe Ser Val Val Lys Arg 
                325                 330                 335     
Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro 
            340                 345                 350         
Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu 
        355                 360                 365             
Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala 
    370                 375                 380                 
Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
385                 390                 395                 400 
Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
                405                 410                 415     
Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
            420                 425                 430         
Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
        435                 440                 445             
Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
    450                 455                 460                 
Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
465                 470                 475                 480 
His Met Gln Ala Leu Pro Pro Arg 
                485             

<210> 53
<211> 1467
<212> DNA
<213> Artificial Sequence


<220> 
<223> Humanized anti-CD19 CAR nucleotide sequence

<400> 53
atggccctgc ctgtgacagc tctgctgctg cctcttgctc tgcttctgca tgctgctaga      60

cctcaggttc agctgcagca atggggagcc ggactgctga agccttctga gacactgtct     120

ctgacctgtg ccgtgtatgg cgtgtccctg cctgattacg gcgtgtcctg gattagacag     180

cctcctggca aaggcctgga atggctggga gtgatctggg gcagcgagac aacctactac     240

agcagcagcc tgaagtccgt gaccatcagc gtggacacca gcaagaacca gttctccctg     300

aagctgtcta gcgtgacagc cgccgatacc gccgtgtact actgtgccag acactactac     360

tacggcggca gctacgccat ggattattgg ggccagggca ccacagtgac agtttctagc     420

ggaggcggag gaagtggtgg cggaggttct ggcggcggag gatctgatat ccagatgaca     480

cagagcccta gcagcctgtc tgcctctgtg ggcgatagag tgaccattac ctgcagagcc     540

agccaggaca tcagcaagta cctgaactgg tatcagcaga agcccggcaa ggcccctaag     600

ctgctgatct accacacaag cagactgcac agcggcgtgc caagcagatt ttctggcagc     660

ggctctggca ccgacttcac cttcaccatt tctagcctgc agcctgagga tatcgccacc     720

tactattgcc agcagggcaa caccctgcct tacacctttg gcggaggcac caaggtggaa     780

atcaagacca ccacaccagc tcctcggcct ccaactcctg ctcctacaat tgcctctcag     840

cctctgagcc tgaggcctga agcttgtaga cctgctgctg gcggagccgt gcataccaga     900

ggactggatt tcgcctgcga catcatctca ttctttctgg ccctgaccag cacagccctg     960

ctgtttctgc tgttctttct gacactgcgg ttcagcgtgg tcaagcgggg cagaaagaag    1020

ctgctgtaca tcttcaagca gcccttcatg cggcccgtgc agacaacaca agaggaagat    1080

ggctgctcct gcagattccc cgaggaagaa gaaggcggct gcgagctgag agtgaagttc    1140

tccagatctg ccgacgctcc tgcttatcag cagggccaga accagctgta caacgagctg    1200

aatctgggga gaagagaaga gtacgacgtg ctggataagc ggagaggcag agatcctgag    1260

atgggcggca agcccagacg gaagaatcct caagagggcc tgtataatga gctgcagaaa    1320

gacaagatgg ccgaggccta cagcgagatc ggaatgaagg gcgagcgcag aagaggcaaa    1380

ggacacgatg gactgtacca gggcctgagc acagccacca aggataccta tgatgccctg    1440

cacatgcagg ccctgccacc tagataa                                        1467


<210> 54
<211> 9066
<212> DNA
<213> Artificial Sequence


<220> 
<223> Vector sequence

<400> 54
gtcgacggat cgggagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg       60

atgccgcata gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt      120

gcgcgagcaa aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc      180

tgcttagggt taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcgttgac      240

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat      300

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg      360

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt      420

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag      480

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc      540

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag      600

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt      660

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc      720

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg      780

gcggtaggcg tgtacggtgg gaggtctata taagcagcgc gttttgcctg tactgggtct      840

ctctggttag accagatctg agcctgggag ctctctggct aactagggaa cccactgctt      900

aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac      960

tctggtaact agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtggc     1020

gcccgaacag ggacttgaaa gcgaaaggga aaccagagga gctctctcga cgcaggactc     1080

ggcttgctga agcgcgcacg gcaagaggcg aggggcggcg actggtgagt acgccaaaaa     1140

ttttgactag cggaggctag aaggagagag atgggtgcga gagcgtcagt attaagcggg     1200

ggagaattag atcgcgatgg gaaaaaattc ggttaaggcc agggggaaag aaaaaatata     1260

aattaaaaca tatagtatgg gcaagcaggg agctagaacg attcgcagtt aatcctggcc     1320

tgttagaaac atcagaaggc tgtagacaaa tactgggaca gctacaacca tcccttcaga     1380

caggatcaga agaacttaga tcattatata atacagtagc aaccctctat tgtgtgcatc     1440

aaaggataga gataaaagac accaaggaag ctttagacaa gatagaggaa gagcaaaaca     1500

aaagtaagac caccgcacag caagcggccg gccgctgatc ttcagacctg gaggaggaga     1560

tatgagggac aattggagaa gtgaattata taaatataaa gtagtaaaaa ttgaaccatt     1620

aggagtagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa gagcagtggg     1680

aataggagct ttgttccttg ggttcttggg agcagcagga agcactatgg gcgcagcgtc     1740

aatgacgctg acggtacagg ccagacaatt attgtctggt atagtgcagc agcagaacaa     1800

tttgctgagg gctattgagg cgcaacagca tctgttgcaa ctcacagtct ggggcatcaa     1860

gcagctccag gcaagaatcc tggctgtgga aagataccta aaggatcaac agctcctggg     1920

gatttggggt tgctctggaa aactcatttg caccactgct gtgccttgga atgctagttg     1980

gagtaataaa tctctggaac agatttggaa tcacacgacc tggatggagt gggacagaga     2040

aattaacaat tacacaagct taatacactc cttaattgaa gaatcgcaaa accagcaaga     2100

aaagaatgaa caagaattat tggaattaga taaatgggca agtttgtgga attggtttaa     2160

cataacaaat tggctgtggt atataaaatt attcataatg atagtaggag gcttggtagg     2220

tttaagaata gtttttgctg tactttctat agtgaataga gttaggcagg gatattcacc     2280

attatcgttt cagacccacc tcccaacccc gaggggaccc gacaggcccg aaggaataga     2340

agaagaaggt ggagagagag acagagacag atccattcga ttagtgaacg gatcggcact     2400

gcgtgcgcca attctgcaga caaatggcag tattcatcca caattttaaa agaaaagggg     2460

ggattggggg gtacagtgca ggggaaagaa tagtagacat aatagcaaca gacatacaaa     2520

ctaaagaatt acaaaaacaa attacaaaaa ttcaaaattt tcgggtttat tacagggaca     2580

gcagagatcc agtttggtta gtaccgggcc cgctctagcg tgaggctccg gtgcccgtca     2640

gtgggcagag cgcacatcgc ccacagtccc cgagaagttg gggggagggg tcggcaattg     2700

aaccggtgcc tagagaaggt ggcgcggggt aaactgggaa agtgatgtcg tgtactggct     2760

ccgccttttt cccgagggtg ggggagaacc gtatataagt gcagtagtcg ccgtgaacgt     2820

tctttttcgc aacgggtttg ccgccagaac acaggtaagt gccgtgtgtg gttcccgcgg     2880

gcctggcctc tttacgggtt atggcccttg cgtgccttga attacttcca cctggctgca     2940

gtacgtgatt cttgatcccg agcttcgggt tggaagtggg tgggagagtt cgaggccttg     3000

cgcttaagga gccccttcgc ctcgtgcttg agttgaggcc tggcctgggc gctggggccg     3060

ccgcgtgcga atctggtggc accttcgcgc ctgtctcgct gctttcgata agtctctagc     3120

catttaaaat ttttgatgac ctgctgcgac gctttttttc tggcaagata gtcttgtaaa     3180

tgcgggccaa gatctgcaca ctggtatttc ggtttttggg gccgcgggcg gcgacggggc     3240

ccgtgcgtcc cagcgcacat gttcggcgag gcggggcctg cgagcgcggc caccgagaat     3300

cggacggggg tagtctcaag ctggccggcc tgctctggtg cctggcctcg cgccgccgtg     3360

tatcgccccg ccctgggcgg caaggctggc ccggtcggca ccagttgcgt gagcggaaag     3420

atggccgctt cccggccctg ctgcagggag ctcaaaatgg aggacgcggc gctcgggaga     3480

gcgggcgggt gagtcaccca cacaaaggaa aagggccttt ccgtcctcag ccgtcgcttc     3540

atgtgactcc acggagtacc gggcgccgtc caggcacctc gattagttct cgagcttttg     3600

gagtacgtcg tctttaggtt ggggggaggg gttttatgcg atggagtttc cccacactga     3660

gtgggtggag actgaagtta ggccagcttg gcacttgatg taattctcct tggaatttgc     3720

cctttttgag tttggatctt ggttcattct caagcctcag acagtggttc aaagtttttt     3780

tcttccattt caggtgtcgt gagcggccgc tgagttaact attatggccc tgcctgtgac     3840

agctctgctg ctgcctcttg ctctgcttct gcatgctgct agacctcagg ttcagctgca     3900

gcaatgggga gccggactgc tgaagccttc tgagacactg tctctgacct gtgccgtcag     3960

cggagtgtct ctgcctgatt acggcgtgtc ctggatcaga cagcctcctg gcaaaggact     4020

ggaatggctg ggagtgatct ggggcagcga gacaacctac tacagcagca gcctgaagtc     4080

cgtgaccatc atcaaggaca ccagcaagaa ccagttctac tactacggcg gcagctacgc     4140

catggattat tggggccagg gcaccacagt gacagtttct agcggaggcg gaggaagtgg     4200

tggcggaggt tctggcggcg gaggatctga tatccagatg acacagagcc ctagcagcct     4260

gtctgcctct gtgggcgata gagtgaccat tacctgcaga gccagccagg acatctccaa     4320

gtacctgaac tggtatcagc agaagcccgg caaggcccct aagctgctga tctaccacac     4380

aagcagactg cacagcggcg tgccaagcag attttctggc agcggctctg gcaccgactt     4440

caccttcacc atttctagcc tgcagcctga ggatatcgcc acctactatt gccagcaggg     4500

caacaccctg ccttacacct ttggcggagg caccaaggtg gaaatcaaga ccaccacacc     4560

agctcctcgg cctccaactc ctgctcctac aattgcctct cagcctctga gcctgaggcc     4620

tgaagcttgt agacctgctg ctggcggagc cgtgcatacc agaggactgg atttcgcctg     4680

cgacatctac atttgggccc ctctggctgg aacatgtggc gtgctgctgc tctccctggt     4740

catcaccctg tactgcaagc ggggcagaaa gaagctgctg tacatcttca agcagccctt     4800

catgcggccc gtgcagacaa cacaagagga agatggctgc tcctgcagat tccccgagga     4860

agaagaaggc ggctgcgagc tgagagtgaa gttctccaga tctgccgacg ctcctgccta     4920

tcagcagggc cagaatcagc tgtacaacga gctgaatctg gggcgcagag aagagtacga     4980

cgtgctggac aagagaaggg gcagagatcc tgagatgggc ggcaagccca gacggaagaa     5040

tcctcaagag ggcctgtata atgagctgca gaaagacaag atggccgagg cctacagcga     5100

gatcggaatg aagggcgaac gcagaagagg caagggccac gatggactgt atcagggcct     5160

gagcacagcc accaaggata cctatgatgc cctgcacatg caggccctgc cacctagata     5220

agatccgccc ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag     5280

gccggtgtgc gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga     5340

gggcccggaa acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg     5400

ccaaaggaat gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt     5460

gaagacaaac aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca     5520

ggtgcctctg cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc     5580

agtgccacgt tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat     5640

tcaacaaggg gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc     5700

ctcggtacac atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga     5760

accacgggga cgtggttttc ctttgaaaaa cacgatgata atatggccac aaccatggtg     5820

agcaagggcg aggagctgtt caccggggtg gtgcccatcc tggtcgagct ggacggcgac     5880

gtaaacggcc acaagttcag cgtgtccggc gagggcgagg gcgatgccac ctacggcaag     5940

ctgaccctga agttcatctg caccaccggc aagctgcccg tgccctggcc caccctcgtg     6000

accaccctga cctacggcgt gcagtgcttc agccgctacc ccgaccacat gaagcagcac     6060

gacttcttca agtccgccat gcccgaaggc tacgtccagg agcgcaccat cttcttcaag     6120

gacgacggca actacaagac ccgcgccgag gtgaagttcg agggcgacac cctggtgaac     6180

cgcatcgagc tgaagggcat cgacttcaag gaggacggca acatcctggg gcacaagctg     6240

gagtacaact acaacagcca caacgtctat atcatggccg acaagcagaa gaacggcatc     6300

aaggtgaact tcaagatccg ccacaacatc gaggacggca gcgtgcagct cgccgaccac     6360

taccagcaga acacccccat cggcgacggc cccgtgctgc tgcccgacaa ccactacctg     6420

agcacccagt ccgccctgag caaagacccc aacgagaagc gcgatcacat ggtcctgctg     6480

gagttcgtga ccgccgccgg gatcactctc ggcatggacg agctgtacaa gtaaagcggc     6540

cgcatcgata ccgtcgacct cgatcgagac ctagaaaaac atggagcaat cacaagtagc     6600

aatacagcag ctaccaatgc tgattgtgcc tggctagaag cacaagagga ggaggaggtg     6660

ggttttccag tcacacctca ggtaccttta agaccaatga cttacaaggc agctgtagat     6720

cttagccact ttttaaaaga aaagggggga ctggaagggc taattcactc ccaacgaaga     6780

caagatatcc ttgatctgtg gatctaccac acacaaggct acttccctga ttggcagaac     6840

tacacaccag ggccagggat cagatatcca ctgacctttg gatggtgcta caagctagta     6900

ccagttgagc aagagaaggt agaagaagcc aatgaaggag agaacacccg cttgttacac     6960

cctgtgagcc tgcatgggat ggatgacccg gagagagaag tattagagtg gaggtttgac     7020

agccgcctag catttcatca catggcccga gagctgcatc cggactgtac tgggtctctc     7080

tggttagacc agatctgagc ctgggagctc tctggctaac tagggaaccc actgcttaag     7140

cctcaataaa gcttgccttg agtgcttcaa gtagtgtgtg cccgtctgtt gtgtgactct     7200

ggtaactaga gatccctcag acccttttag tcagtgtgga aaatctctag cagcatgtga     7260

gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat     7320

aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac     7380

ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct     7440

gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg     7500

ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg     7560

ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt     7620

cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg     7680

attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac     7740

ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga     7800

aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt     7860

gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt     7920

tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga     7980

ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc     8040

taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct     8100

atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt cgtgtagata     8160

actacgatac gggagggctt accatctggc cccagtgctg caatgatacc gcgagaccca     8220

cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc cgagcgcaga     8280

agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg ggaagctaga     8340

gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac aggcatcgtg     8400

gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg atcaaggcga     8460

gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt     8520

gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact gcataattct     8580

cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc aaccaagtca     8640

ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat acgggataat     8700

accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga     8760

aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac tcgtgcaccc     8820

aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa aacaggaagg     8880

caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact catactcttc     8940

ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg atacatattt     9000

gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg aaaagtgcca     9060

cctgac                                                                9066


<210> 55
<211> 9126
<212> DNA
<213> Artificial Sequence


<220> 
<223> Vector sequence

<400> 55
gtcgacggat cgggagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg       60

atgccgcata gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt      120

gcgcgagcaa aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc      180

tgcttagggt taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcgttgac      240

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat      300

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg      360

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt      420

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag      480

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc      540

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag      600

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt      660

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc      720

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg      780

gcggtaggcg tgtacggtgg gaggtctata taagcagcgc gttttgcctg tactgggtct      840

ctctggttag accagatctg agcctgggag ctctctggct aactagggaa cccactgctt      900

aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac      960

tctggtaact agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtggc     1020

gcccgaacag ggacttgaaa gcgaaaggga aaccagagga gctctctcga cgcaggactc     1080

ggcttgctga agcgcgcacg gcaagaggcg aggggcggcg actggtgagt acgccaaaaa     1140

ttttgactag cggaggctag aaggagagag atgggtgcga gagcgtcagt attaagcggg     1200

ggagaattag atcgcgatgg gaaaaaattc ggttaaggcc agggggaaag aaaaaatata     1260

aattaaaaca tatagtatgg gcaagcaggg agctagaacg attcgcagtt aatcctggcc     1320

tgttagaaac atcagaaggc tgtagacaaa tactgggaca gctacaacca tcccttcaga     1380

caggatcaga agaacttaga tcattatata atacagtagc aaccctctat tgtgtgcatc     1440

aaaggataga gataaaagac accaaggaag ctttagacaa gatagaggaa gagcaaaaca     1500

aaagtaagac caccgcacag caagcggccg gccgctgatc ttcagacctg gaggaggaga     1560

tatgagggac aattggagaa gtgaattata taaatataaa gtagtaaaaa ttgaaccatt     1620

aggagtagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa gagcagtggg     1680

aataggagct ttgttccttg ggttcttggg agcagcagga agcactatgg gcgcagcgtc     1740

aatgacgctg acggtacagg ccagacaatt attgtctggt atagtgcagc agcagaacaa     1800

tttgctgagg gctattgagg cgcaacagca tctgttgcaa ctcacagtct ggggcatcaa     1860

gcagctccag gcaagaatcc tggctgtgga aagataccta aaggatcaac agctcctggg     1920

gatttggggt tgctctggaa aactcatttg caccactgct gtgccttgga atgctagttg     1980

gagtaataaa tctctggaac agatttggaa tcacacgacc tggatggagt gggacagaga     2040

aattaacaat tacacaagct taatacactc cttaattgaa gaatcgcaaa accagcaaga     2100

aaagaatgaa caagaattat tggaattaga taaatgggca agtttgtgga attggtttaa     2160

cataacaaat tggctgtggt atataaaatt attcataatg atagtaggag gcttggtagg     2220

tttaagaata gtttttgctg tactttctat agtgaataga gttaggcagg gatattcacc     2280

attatcgttt cagacccacc tcccaacccc gaggggaccc gacaggcccg aaggaataga     2340

agaagaaggt ggagagagag acagagacag atccattcga ttagtgaacg gatcggcact     2400

gcgtgcgcca attctgcaga caaatggcag tattcatcca caattttaaa agaaaagggg     2460

ggattggggg gtacagtgca ggggaaagaa tagtagacat aatagcaaca gacatacaaa     2520

ctaaagaatt acaaaaacaa attacaaaaa ttcaaaattt tcgggtttat tacagggaca     2580

gcagagatcc agtttggtta gtaccgggcc cgctctagcg tgaggctccg gtgcccgtca     2640

gtgggcagag cgcacatcgc ccacagtccc cgagaagttg gggggagggg tcggcaattg     2700

aaccggtgcc tagagaaggt ggcgcggggt aaactgggaa agtgatgtcg tgtactggct     2760

ccgccttttt cccgagggtg ggggagaacc gtatataagt gcagtagtcg ccgtgaacgt     2820

tctttttcgc aacgggtttg ccgccagaac acaggtaagt gccgtgtgtg gttcccgcgg     2880

gcctggcctc tttacgggtt atggcccttg cgtgccttga attacttcca cctggctgca     2940

gtacgtgatt cttgatcccg agcttcgggt tggaagtggg tgggagagtt cgaggccttg     3000

cgcttaagga gccccttcgc ctcgtgcttg agttgaggcc tggcctgggc gctggggccg     3060

ccgcgtgcga atctggtggc accttcgcgc ctgtctcgct gctttcgata agtctctagc     3120

catttaaaat ttttgatgac ctgctgcgac gctttttttc tggcaagata gtcttgtaaa     3180

tgcgggccaa gatctgcaca ctggtatttc ggtttttggg gccgcgggcg gcgacggggc     3240

ccgtgcgtcc cagcgcacat gttcggcgag gcggggcctg cgagcgcggc caccgagaat     3300

cggacggggg tagtctcaag ctggccggcc tgctctggtg cctggcctcg cgccgccgtg     3360

tatcgccccg ccctgggcgg caaggctggc ccggtcggca ccagttgcgt gagcggaaag     3420

atggccgctt cccggccctg ctgcagggag ctcaaaatgg aggacgcggc gctcgggaga     3480

gcgggcgggt gagtcaccca cacaaaggaa aagggccttt ccgtcctcag ccgtcgcttc     3540

atgtgactcc acggagtacc gggcgccgtc caggcacctc gattagttct cgagcttttg     3600

gagtacgtcg tctttaggtt ggggggaggg gttttatgcg atggagtttc cccacactga     3660

gtgggtggag actgaagtta ggccagcttg gcacttgatg taattctcct tggaatttgc     3720

cctttttgag tttggatctt ggttcattct caagcctcag acagtggttc aaagtttttt     3780

tcttccattt caggtgtcgt gagcggccgc tgagttaact attatggccc tgcctgtgac     3840

agctctgctg ctgcctcttg ctctgcttct gcatgctgct agacctcagg ttcagctgca     3900

gcaatgggga gccggactgc tgaagccttc tgagacactg tctctgacct gtgccgtgta     3960

tggcgtgtcc ctgcctgatt acggcgtgtc ctggattaga cagcctcctg gcaaaggcct     4020

ggaatggctg ggagtgatct ggggcagcga gacaacctac tacagcagca gcctgaagtc     4080

cgtgaccatc agcgtggaca ccagcaagaa ccagttctcc ctgaagctgt ctagcgtgac     4140

agccgccgat accgccgtgt actactgtgc cagacactac tactacggcg gcagctacgc     4200

catggattat tggggccagg gcaccacagt gacagtttct agcggaggcg gaggaagtgg     4260

tggcggaggt tctggcggcg gaggatctga tatccagatg acacagagcc ctagcagcct     4320

gtctgcctct gtgggcgata gagtgaccat tacctgcaga gccagccagg acatcagcaa     4380

gtacctgaac tggtatcagc agaagcccgg caaggcccct aagctgctga tctaccacac     4440

aagcagactg cacagcggcg tgccaagcag attttctggc agcggctctg gcaccgactt     4500

caccttcacc atttctagcc tgcagcctga ggatatcgcc acctactatt gccagcaggg     4560

caacaccctg ccttacacct ttggcggagg caccaaggtg gaaatcaaga ccaccacacc     4620

agctcctcgg cctccaactc ctgctcctac aattgcctct cagcctctga gcctgaggcc     4680

tgaagcttgt agacctgctg ctggcggagc cgtgcatacc agaggactgg atttcgcctg     4740

cgacatctac atttgggccc ctctggctgg aacatgtggc gtgctgctgc tcagcctggt     4800

catcaccctg tactgcaagc ggggcagaaa gaagctgctg tacatcttca agcagccctt     4860

catgcggccc gtgcagacaa cacaagagga agatggctgc tcctgcagat tccccgagga     4920

agaagaaggc ggctgcgagc tgagagtgaa gttctccaga tctgccgacg ctcctgctta     4980

tcagcagggc cagaaccagc tgtacaacga gctgaatctg gggagaagag aagagtacga     5040

cgtgctggat aagcggagag gcagagatcc tgagatgggc ggcaagccca gacggaagaa     5100

tcctcaagag ggcctgtata atgagctgca gaaagacaag atggccgagg cctacagcga     5160

gatcggaatg aagggcgagc gcagaagagg caaaggacac gatggactgt accagggcct     5220

gagcacagcc accaaggata cctatgatgc cctgcacatg caggccctgc cacctagata     5280

agatccgccc ctctccctcc ccccccccta acgttactgg ccgaagccgc ttggaataag     5340

gccggtgtgc gtttgtctat atgttatttt ccaccatatt gccgtctttt ggcaatgtga     5400

gggcccggaa acctggccct gtcttcttga cgagcattcc taggggtctt tcccctctcg     5460

ccaaaggaat gcaaggtctg ttgaatgtcg tgaaggaagc agttcctctg gaagcttctt     5520

gaagacaaac aacgtctgta gcgacccttt gcaggcagcg gaacccccca cctggcgaca     5580

ggtgcctctg cggccaaaag ccacgtgtat aagatacacc tgcaaaggcg gcacaacccc     5640

agtgccacgt tgtgagttgg atagttgtgg aaagagtcaa atggctctcc tcaagcgtat     5700

tcaacaaggg gctgaaggat gcccagaagg taccccattg tatgggatct gatctggggc     5760

ctcggtacac atgctttaca tgtgtttagt cgaggttaaa aaaacgtcta ggccccccga     5820

accacgggga cgtggttttc ctttgaaaaa cacgatgata atatggccac aaccatggtg     5880

agcaagggcg aggagctgtt caccggggtg gtgcccatcc tggtcgagct ggacggcgac     5940

gtaaacggcc acaagttcag cgtgtccggc gagggcgagg gcgatgccac ctacggcaag     6000

ctgaccctga agttcatctg caccaccggc aagctgcccg tgccctggcc caccctcgtg     6060

accaccctga cctacggcgt gcagtgcttc agccgctacc ccgaccacat gaagcagcac     6120

gacttcttca agtccgccat gcccgaaggc tacgtccagg agcgcaccat cttcttcaag     6180

gacgacggca actacaagac ccgcgccgag gtgaagttcg agggcgacac cctggtgaac     6240

cgcatcgagc tgaagggcat cgacttcaag gaggacggca acatcctggg gcacaagctg     6300

gagtacaact acaacagcca caacgtctat atcatggccg acaagcagaa gaacggcatc     6360

aaggtgaact tcaagatccg ccacaacatc gaggacggca gcgtgcagct cgccgaccac     6420

taccagcaga acacccccat cggcgacggc cccgtgctgc tgcccgacaa ccactacctg     6480

agcacccagt ccgccctgag caaagacccc aacgagaagc gcgatcacat ggtcctgctg     6540

gagttcgtga ccgccgccgg gatcactctc ggcatggacg agctgtacaa gtaaagcggc     6600

cgcatcgata ccgtcgacct cgatcgagac ctagaaaaac atggagcaat cacaagtagc     6660

aatacagcag ctaccaatgc tgattgtgcc tggctagaag cacaagagga ggaggaggtg     6720

ggttttccag tcacacctca ggtaccttta agaccaatga cttacaaggc agctgtagat     6780

cttagccact ttttaaaaga aaagggggga ctggaagggc taattcactc ccaacgaaga     6840

caagatatcc ttgatctgtg gatctaccac acacaaggct acttccctga ttggcagaac     6900

tacacaccag ggccagggat cagatatcca ctgacctttg gatggtgcta caagctagta     6960

ccagttgagc aagagaaggt agaagaagcc aatgaaggag agaacacccg cttgttacac     7020

cctgtgagcc tgcatgggat ggatgacccg gagagagaag tattagagtg gaggtttgac     7080

agccgcctag catttcatca catggcccga gagctgcatc cggactgtac tgggtctctc     7140

tggttagacc agatctgagc ctgggagctc tctggctaac tagggaaccc actgcttaag     7200

cctcaataaa gcttgccttg agtgcttcaa gtagtgtgtg cccgtctgtt gtgtgactct     7260

ggtaactaga gatccctcag acccttttag tcagtgtgga aaatctctag cagcatgtga     7320

gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat     7380

aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac     7440

ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct     7500

gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg     7560

ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg     7620

ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt     7680

cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg     7740

attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac     7800

ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga     7860

aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt     7920

gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt     7980

tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga     8040

ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc     8100

taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct     8160

atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt cgtgtagata     8220

actacgatac gggagggctt accatctggc cccagtgctg caatgatacc gcgagaccca     8280

cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc cgagcgcaga     8340

agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg ggaagctaga     8400

gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac aggcatcgtg     8460

gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg atcaaggcga     8520

gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt     8580

gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact gcataattct     8640

cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc aaccaagtca     8700

ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat acgggataat     8760

accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga     8820

aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac tcgtgcaccc     8880

aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa aacaggaagg     8940

caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact catactcttc     9000

ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg atacatattt     9060

gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg aaaagtgcca     9120

cctgac                                                                9126


<210> 56
<211> 7829
<212> DNA
<213> Artificial Sequence


<220> 
<223> Vector sequence

<400> 56
gtcgacggat cgggagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg       60

atgccgcata gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt      120

gcgcgagcaa aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc      180

tgcttagggt taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcgttgac      240

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat      300

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg      360

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt      420

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag      480

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc      540

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag      600

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt      660

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc      720

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg      780

gcggtaggcg tgtacggtgg gaggtctata taagcagcgc gttttgcctg tactgggtct      840

ctctggttag accagatctg agcctgggag ctctctggct aactagggaa cccactgctt      900

aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac      960

tctggtaact agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtggc     1020

gcccgaacag ggacttgaaa gcgaaaggga aaccagagga gctctctcga cgcaggactc     1080

ggcttgctga agcgcgcacg gcaagaggcg aggggcggcg actggtgagt acgccaaaaa     1140

ttttgactag cggaggctag aaggagagag atgggtgcga gagcgtcagt attaagcggg     1200

ggagaattag atcgcgatgg gaaaaaattc ggttaaggcc agggggaaag aaaaaatata     1260

aattaaaaca tatagtatgg gcaagcaggg agctagaacg attcgcagtt aatcctggcc     1320

tgttagaaac atcagaaggc tgtagacaaa tactgggaca gctacaacca tcccttcaga     1380

caggatcaga agaacttaga tcattatata atacagtagc aaccctctat tgtgtgcatc     1440

aaaggataga gataaaagac accaaggaag ctttagacaa gatagaggaa gagcaaaaca     1500

aaagtaagac caccgcacag caagcggccg gccgctgatc ttcagacctg gaggaggaga     1560

tatgagggac aattggagaa gtgaattata taaatataaa gtagtaaaaa ttgaaccatt     1620

aggagtagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa gagcagtggg     1680

aataggagct ttgttccttg ggttcttggg agcagcagga agcactatgg gcgcagcgtc     1740

aatgacgctg acggtacagg ccagacaatt attgtctggt atagtgcagc agcagaacaa     1800

tttgctgagg gctattgagg cgcaacagca tctgttgcaa ctcacagtct ggggcatcaa     1860

gcagctccag gcaagaatcc tggctgtgga aagataccta aaggatcaac agctcctggg     1920

gatttggggt tgctctggaa aactcatttg caccactgct gtgccttgga atgctagttg     1980

gagtaataaa tctctggaac agatttggaa tcacacgacc tggatggagt gggacagaga     2040

aattaacaat tacacaagct taatacactc cttaattgaa gaatcgcaaa accagcaaga     2100

aaagaatgaa caagaattat tggaattaga taaatgggca agtttgtgga attggtttaa     2160

cataacaaat tggctgtggt atataaaatt attcataatg atagtaggag gcttggtagg     2220

tttaagaata gtttttgctg tactttctat agtgaataga gttaggcagg gatattcacc     2280

attatcgttt cagacccacc tcccaacccc gaggggaccc gacaggcccg aaggaataga     2340

agaagaaggt ggagagagag acagagacag atccattcga ttagtgaacg gatcggcact     2400

gcgtgcgcca attctgcaga caaatggcag tattcatcca caattttaaa agaaaagggg     2460

ggattggggg gtacagtgca ggggaaagaa tagtagacat aatagcaaca gacatacaaa     2520

ctaaagaatt acaaaaacaa attacaaaaa ttcaaaattt tcgggtttat tacagggaca     2580

gcagagatcc agtttggtta gtaccgggcc cgctctagcg tgaggctccg gtgcccgtca     2640

gtgggcagag cgcacatcgc ccacagtccc cgagaagttg gggggagggg tcggcaattg     2700

aaccggtgcc tagagaaggt ggcgcggggt aaactgggaa agtgatgtcg tgtactggct     2760

ccgccttttt cccgagggtg ggggagaacc gtatataagt gcagtagtcg ccgtgaacgt     2820

tctttttcgc aacgggtttg ccgccagaac acaggtaagt gccgtgtgtg gttcccgcgg     2880

gcctggcctc tttacgggtt atggcccttg cgtgccttga attacttcca cctggctgca     2940

gtacgtgatt cttgatcccg agcttcgggt tggaagtggg tgggagagtt cgaggccttg     3000

cgcttaagga gccccttcgc ctcgtgcttg agttgaggcc tggcctgggc gctggggccg     3060

ccgcgtgcga atctggtggc accttcgcgc ctgtctcgct gctttcgata agtctctagc     3120

catttaaaat ttttgatgac ctgctgcgac gctttttttc tggcaagata gtcttgtaaa     3180

tgcgggccaa gatctgcaca ctggtatttc ggtttttggg gccgcgggcg gcgacggggc     3240

ccgtgcgtcc cagcgcacat gttcggcgag gcggggcctg cgagcgcggc caccgagaat     3300

cggacggggg tagtctcaag ctggccggcc tgctctggtg cctggcctcg cgccgccgtg     3360

tatcgccccg ccctgggcgg caaggctggc ccggtcggca ccagttgcgt gagcggaaag     3420

atggccgctt cccggccctg ctgcagggag ctcaaaatgg aggacgcggc gctcgggaga     3480

gcgggcgggt gagtcaccca cacaaaggaa aagggccttt ccgtcctcag ccgtcgcttc     3540

atgtgactcc acggagtacc gggcgccgtc caggcacctc gattagttct cgagcttttg     3600

gagtacgtcg tctttaggtt ggggggaggg gttttatgcg atggagtttc cccacactga     3660

gtgggtggag actgaagtta ggccagcttg gcacttgatg taattctcct tggaatttgc     3720

cctttttgag tttggatctt ggttcattct caagcctcag acagtggttc aaagtttttt     3780

tcttccattt caggtgtcgt gagcggccgc tgagttaact attctagagt acccgggcta     3840

gatggcattg cctgttacag ctctgctgct gcctctggct ctgcttctgc atgctgctag     3900

acctcaggtt cagctgcagc aatggggagc cggactgctg aagccttctg agacactgtc     3960

tctgacctgt gccgtcagcg gagtgtctct gcctgattac ggcgtgtcct ggatcagaca     4020

gcctcctggc aaaggactgg aatggctggg agtgatctgg ggcagcgaga caacctacta     4080

cagcagcagc ctgaagtccg tgaccatcat caaggacacc agcaagaacc agttcttcct     4140

gaagctgagc agcgtgacag ccgccgatac agccgtgtac tactgcgcca gacactacta     4200

ctacggcggc agctacgcca tggattattg gggccagggc accacagtga cagtttctag     4260

cggaggcgga ggaagtggcg gcggaggatc tggcggtggt ggttctgata tccagatgac     4320

acagagccct agcagcctgt ctgcctctgt gggcgataga gtgaccatta cctgtcgggc     4380

cagccaggac atctccaagt acctgaactg gtatcagcag aagcccggca aggcccctaa     4440

gctgctgatc taccacacaa gcagactgca cagcggcgtg ccaagcagat tttctggcag     4500

cggctctggc accgacttca ccttcaccat ttctagcctg cagcctgagg atatcgccac     4560

ctactattgc cagcagggca acaccctgcc ttacaccttt ggcggaggca ccaaggtgga     4620

aatcaagacc accacaccag ctcctcggcc tccaactcct gctcctacaa ttgcctctca     4680

gcctctgagc ctgaggcctg aagcttgtag acctgctgct ggcggagccg tgcataccag     4740

aggactggat ttcgcctgcg acatcatctc attctttctg gccctgacca gcacagccct     4800

gctgtttctg ctgttctttc tgacactgcg gttcagcgtg gtcaagcggg gaagaaagaa     4860

gctgctgtac atcttcaagc agcccttcat gcggcccgtg cagacaacac aagaggaaga     4920

tggctgctcc tgcagattcc ccgaggaaga agaaggcggc tgcgagctga gagtgaagtt     4980

ctctagatct gccgacgctc ccgcctacca gcagggacag aatcagctgt acaacgagct     5040

gaatctgggg cgcagagaag agtacgacgt gctggataag agaagaggca gagatcccga     5100

gatgggcggc aagcctcgga gaaagaatcc tcaagagggc ctctacaatg agctgcagaa     5160

agacaagatg gccgaggcct acagcgagat cggaatgaag ggcgaacgca gaagaggaaa     5220

gggccacgac ggactgtatc agggcctgag cacagccacc aaggatacct atgatgccct     5280

gcacatgcag gccctgcctc caagatgacg ataccgtcga cctcgatcga gacctagaaa     5340

aacatggagc aatcacaagt agcaatacag cagctaccaa tgctgattgt gcctggctag     5400

aagcacaaga ggaggaggag gtgggttttc cagtcacacc tcaggtacct ttaagaccaa     5460

tgacttacaa ggcagctgta gatcttagcc actttttaaa agaaaagggg ggactggaag     5520

ggctaattca ctcccaacga agacaagata tccttgatct gtggatctac cacacacaag     5580

gctacttccc tgattggcag aactacacac cagggccagg gatcagatat ccactgacct     5640

ttggatggtg ctacaagcta gtaccagttg agcaagagaa ggtagaagaa gccaatgaag     5700

gagagaacac ccgcttgtta caccctgtga gcctgcatgg gatggatgac ccggagagag     5760

aagtattaga gtggaggttt gacagccgcc tagcatttca tcacatggcc cgagagctgc     5820

atccggactg tactgggtct ctctggttag accagatctg agcctgggag ctctctggct     5880

aactagggaa cccactgctt aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt     5940

gtgcccgtct gttgtgtgac tctggtaact agagatccct cagacccttt tagtcagtgt     6000

ggaaaatctc tagcagcatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg     6060

ccgcgttgct ggcgtttttc cataggctcc gcccccctga cgagcatcac aaaaatcgac     6120

gctcaagtca gaggtggcga aacccgacag gactataaag ataccaggcg tttccccctg     6180

gaagctccct cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct     6240

ttctcccttc gggaagcgtg gcgctttctc atagctcacg ctgtaggtat ctcagttcgg     6300

tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct     6360

gcgccttatc cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac     6420

tggcagcagc cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt     6480

tcttgaagtg gtggcctaac tacggctaca ctagaagaac agtatttggt atctgcgctc     6540

tgctgaagcc agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca     6600

ccgctggtag cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat     6660

ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac     6720

gttaagggat tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt     6780

aaaaatgaag ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc     6840

aatgcttaat cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg     6900

cctgactccc cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg     6960

ctgcaatgat accgcgagac ccacgctcac cggctccaga tttatcagca ataaaccagc     7020

cagccggaag ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta     7080

ttaattgttg ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg     7140

ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct     7200

ccggttccca acgatcaagg cgagttacat gatcccccat gttgtgcaaa aaagcggtta     7260

gctccttcgg tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg     7320

ttatggcagc actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga     7380

ctggtgagta ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt     7440

gcccggcgtc aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca     7500

ttggaaaacg ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt     7560

cgatgtaacc cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt     7620

ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga     7680

aatgttgaat actcatactc ttcctttttc aatattattg aagcatttat cagggttatt     7740

gtctcatgag cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc     7800

gcacatttcc ccgaaaagtg ccacctgac                                       7829


<210> 57
<211> 9135
<212> DNA
<213> Artificial Sequence


<220> 
<223> Vector sequence

<400> 57
gtcgacggat cgggagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg       60

atgccgcata gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt      120

gcgcgagcaa aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc      180

tgcttagggt taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcgttgac      240

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat      300

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg      360

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt      420

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag      480

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc      540

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag      600

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt      660

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc      720

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg      780

gcggtaggcg tgtacggtgg gaggtctata taagcagcgc gttttgcctg tactgggtct      840

ctctggttag accagatctg agcctgggag ctctctggct aactagggaa cccactgctt      900

aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac      960

tctggtaact agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtggc     1020

gcccgaacag ggacttgaaa gcgaaaggga aaccagagga gctctctcga cgcaggactc     1080

ggcttgctga agcgcgcacg gcaagaggcg aggggcggcg actggtgagt acgccaaaaa     1140

ttttgactag cggaggctag aaggagagag atgggtgcga gagcgtcagt attaagcggg     1200

ggagaattag atcgcgatgg gaaaaaattc ggttaaggcc agggggaaag aaaaaatata     1260

aattaaaaca tatagtatgg gcaagcaggg agctagaacg attcgcagtt aatcctggcc     1320

tgttagaaac atcagaaggc tgtagacaaa tactgggaca gctacaacca tcccttcaga     1380

caggatcaga agaacttaga tcattatata atacagtagc aaccctctat tgtgtgcatc     1440

aaaggataga gataaaagac accaaggaag ctttagacaa gatagaggaa gagcaaaaca     1500

aaagtaagac caccgcacag caagcggccg gccgctgatc ttcagacctg gaggaggaga     1560

tatgagggac aattggagaa gtgaattata taaatataaa gtagtaaaaa ttgaaccatt     1620

aggagtagca cccaccaagg caaagagaag agtggtgcag agagaaaaaa gagcagtggg     1680

aataggagct ttgttccttg ggttcttggg agcagcagga agcactatgg gcgcagcgtc     1740

aatgacgctg acggtacagg ccagacaatt attgtctggt atagtgcagc agcagaacaa     1800

tttgctgagg gctattgagg cgcaacagca tctgttgcaa ctcacagtct ggggcatcaa     1860

gcagctccag gcaagaatcc tggctgtgga aagataccta aaggatcaac agctcctggg     1920

gatttggggt tgctctggaa aactcatttg caccactgct gtgccttgga atgctagttg     1980

gagtaataaa tctctggaac agatttggaa tcacacgacc tggatggagt gggacagaga     2040

aattaacaat tacacaagct taatacactc cttaattgaa gaatcgcaaa accagcaaga     2100

aaagaatgaa caagaattat tggaattaga taaatgggca agtttgtgga attggtttaa     2160

cataacaaat tggctgtggt atataaaatt attcataatg atagtaggag gcttggtagg     2220

tttaagaata gtttttgctg tactttctat agtgaataga gttaggcagg gatattcacc     2280

attatcgttt cagacccacc tcccaacccc gaggggaccc gacaggcccg aaggaataga     2340

agaagaaggt ggagagagag acagagacag atccattcga ttagtgaacg gatcggcact     2400

gcgtgcgcca attctgcaga caaatggcag tattcatcca caattttaaa agaaaagggg     2460

ggattggggg gtacagtgca ggggaaagaa tagtagacat aatagcaaca gacatacaaa     2520

ctaaagaatt acaaaaacaa attacaaaaa ttcaaaattt tcgggtttat tacagggaca     2580

gcagagatcc agtttggtta gtaccgggcc cgctctagcg tgaggctccg gtgcccgtca     2640

gtgggcagag cgcacatcgc ccacagtccc cgagaagttg gggggagggg tcggcaattg     2700

aaccggtgcc tagagaaggt ggcgcggggt aaactgggaa agtgatgtcg tgtactggct     2760

ccgccttttt cccgagggtg ggggagaacc gtatataagt gcagtagtcg ccgtgaacgt     2820

tctttttcgc aacgggtttg ccgccagaac acaggtaagt gccgtgtgtg gttcccgcgg     2880

gcctggcctc tttacgggtt atggcccttg cgtgccttga attacttcca cctggctgca     2940

gtacgtgatt cttgatcccg agcttcgggt tggaagtggg tgggagagtt cgaggccttg     3000

cgcttaagga gccccttcgc ctcgtgcttg agttgaggcc tggcctgggc gctggggccg     3060

ccgcgtgcga atctggtggc accttcgcgc ctgtctcgct gctttcgata agtctctagc     3120

catttaaaat ttttgatgac ctgctgcgac gctttttttc tggcaagata gtcttgtaaa     3180

tgcgggccaa gatctgcaca ctggtatttc ggtttttggg gccgcgggcg gcgacggggc     3240

ccgtgcgtcc cagcgcacat gttcggcgag gcggggcctg cgagcgcggc caccgagaat     3300

cggacggggg tagtctcaag ctggccggcc tgctctggtg cctggcctcg cgccgccgtg     3360

tatcgccccg ccctgggcgg caaggctggc ccggtcggca ccagttgcgt gagcggaaag     3420

atggccgctt cccggccctg ctgcagggag ctcaaaatgg aggacgcggc gctcgggaga     3480

gcgggcgggt gagtcaccca cacaaaggaa aagggccttt ccgtcctcag ccgtcgcttc     3540

atgtgactcc acggagtacc gggcgccgtc caggcacctc gattagttct cgagcttttg     3600

gagtacgtcg tctttaggtt ggggggaggg gttttatgcg atggagtttc cccacactga     3660

gtgggtggag actgaagtta ggccagcttg gcacttgatg taattctcct tggaatttgc     3720

cctttttgag tttggatctt ggttcattct caagcctcag acagtggttc aaagtttttt     3780

tcttccattt caggtgtcgt gagcggccgc tgagttaact attatggccc tgcctgtgac     3840

agctctgctg ctgcctcttg ctctgcttct gcatgctgct agacctcagg ttcagctgca     3900

gcaatgggga gccggactgc tgaagccttc tgagacactg tctctgacct gtgccgtgta     3960

tggcgtgtcc ctgcctgatt acggcgtgtc ctggattaga cagcctcctg gcaaaggcct     4020

ggaatggctg ggagtgatct ggggcagcga gacaacctac tacagcagca gcctgaagtc     4080

cgtgaccatc agcgtggaca ccagcaagaa ccagttctcc ctgaagctgt ctagcgtgac     4140

agccgccgat accgccgtgt actactgtgc cagacactac tactacggcg gcagctacgc     4200

catggattat tggggccagg gcaccacagt gacagtttct agcggaggcg gaggaagtgg     4260

tggcggaggt tctggcggcg gaggatctga tatccagatg acacagagcc ctagcagcct     4320

gtctgcctct gtgggcgata gagtgaccat tacctgcaga gccagccagg acatcagcaa     4380

gtacctgaac tggtatcagc agaagcccgg caaggcccct aagctgctga tctaccacac     4440

aagcagactg cacagcggcg tgccaagcag attttctggc agcggctctg gcaccgactt     4500

caccttcacc atttctagcc tgcagcctga ggatatcgcc acctactatt gccagcaggg     4560

caacaccctg ccttacacct ttggcggagg caccaaggtg gaaatcaaga ccaccacacc     4620

agctcctcgg cctccaactc ctgctcctac aattgcctct cagcctctga gcctgaggcc     4680

tgaagcttgt agacctgctg ctggcggagc cgtgcatacc agaggactgg atttcgcctg     4740

cgacatcatc tcattctttc tggccctgac cagcacagcc ctgctgtttc tgctgttctt     4800

tctgacactg cggttcagcg tggtcaagcg gggcagaaag aagctgctgt acatcttcaa     4860

gcagcccttc atgcggcccg tgcagacaac acaagaggaa gatggctgct cctgcagatt     4920

ccccgaggaa gaagaaggcg gctgcgagct gagagtgaag ttctccagat ctgccgacgc     4980

tcctgcttat cagcagggcc agaaccagct gtacaacgag ctgaatctgg ggagaagaga     5040

agagtacgac gtgctggata agcggagagg cagagatcct gagatgggcg gcaagcccag     5100

acggaagaat cctcaagagg gcctgtataa tgagctgcag aaagacaaga tggccgaggc     5160

ctacagcgag atcggaatga agggcgagcg cagaagaggc aaaggacacg atggactgta     5220

ccagggcctg agcacagcca ccaaggatac ctatgatgcc ctgcacatgc aggccctgcc     5280

acctagataa gatccgcccc tctccctccc ccccccctaa cgttactggc cgaagccgct     5340

tggaataagg ccggtgtgcg tttgtctata tgttattttc caccatattg ccgtcttttg     5400

gcaatgtgag ggcccggaaa cctggccctg tcttcttgac gagcattcct aggggtcttt     5460

cccctctcgc caaaggaatg caaggtctgt tgaatgtcgt gaaggaagca gttcctctgg     5520

aagcttcttg aagacaaaca acgtctgtag cgaccctttg caggcagcgg aaccccccac     5580

ctggcgacag gtgcctctgc ggccaaaagc cacgtgtata agatacacct gcaaaggcgg     5640

cacaacccca gtgccacgtt gtgagttgga tagttgtgga aagagtcaaa tggctctcct     5700

caagcgtatt caacaagggg ctgaaggatg cccagaaggt accccattgt atgggatctg     5760

atctggggcc tcggtacaca tgctttacat gtgtttagtc gaggttaaaa aaacgtctag     5820

gccccccgaa ccacggggac gtggttttcc tttgaaaaac acgatgataa tatggccaca     5880

accatggtga gcaagggcga ggagctgttc accggggtgg tgcccatcct ggtcgagctg     5940

gacggcgacg taaacggcca caagttcagc gtgtccggcg agggcgaggg cgatgccacc     6000

tacggcaagc tgaccctgaa gttcatctgc accaccggca agctgcccgt gccctggccc     6060

accctcgtga ccaccctgac ctacggcgtg cagtgcttca gccgctaccc cgaccacatg     6120

aagcagcacg acttcttcaa gtccgccatg cccgaaggct acgtccagga gcgcaccatc     6180

ttcttcaagg acgacggcaa ctacaagacc cgcgccgagg tgaagttcga gggcgacacc     6240

ctggtgaacc gcatcgagct gaagggcatc gacttcaagg aggacggcaa catcctgggg     6300

cacaagctgg agtacaacta caacagccac aacgtctata tcatggccga caagcagaag     6360

aacggcatca aggtgaactt caagatccgc cacaacatcg aggacggcag cgtgcagctc     6420

gccgaccact accagcagaa cacccccatc ggcgacggcc ccgtgctgct gcccgacaac     6480

cactacctga gcacccagtc cgccctgagc aaagacccca acgagaagcg cgatcacatg     6540

gtcctgctgg agttcgtgac cgccgccggg atcactctcg gcatggacga gctgtacaag     6600

taaagcggcc gcatcgatac cgtcgacctc gatcgagacc tagaaaaaca tggagcaatc     6660

acaagtagca atacagcagc taccaatgct gattgtgcct ggctagaagc acaagaggag     6720

gaggaggtgg gttttccagt cacacctcag gtacctttaa gaccaatgac ttacaaggca     6780

gctgtagatc ttagccactt tttaaaagaa aaggggggac tggaagggct aattcactcc     6840

caacgaagac aagatatcct tgatctgtgg atctaccaca cacaaggcta cttccctgat     6900

tggcagaact acacaccagg gccagggatc agatatccac tgacctttgg atggtgctac     6960

aagctagtac cagttgagca agagaaggta gaagaagcca atgaaggaga gaacacccgc     7020

ttgttacacc ctgtgagcct gcatgggatg gatgacccgg agagagaagt attagagtgg     7080

aggtttgaca gccgcctagc atttcatcac atggcccgag agctgcatcc ggactgtact     7140

gggtctctct ggttagacca gatctgagcc tgggagctct ctggctaact agggaaccca     7200

ctgcttaagc ctcaataaag cttgccttga gtgcttcaag tagtgtgtgc ccgtctgttg     7260

tgtgactctg gtaactagag atccctcaga cccttttagt cagtgtggaa aatctctagc     7320

agcatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg     7380

tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg     7440

tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag ctccctcgtg     7500

cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga     7560

agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc     7620

tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc cttatccggt     7680

aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc agcagccact     7740

ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt gaagtggtgg     7800

cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct gaagccagtt     7860

accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt     7920

ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct     7980

ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg     8040

gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt     8100

aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg cttaatcagt     8160

gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg actccccgtc     8220

gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg     8280

cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc     8340

gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg     8400

gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc cattgctaca     8460

ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga     8520

tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc cttcggtcct     8580

ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat ggcagcactg     8640

cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca     8700

accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata     8760

cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct     8820

tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact     8880

cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa     8940

acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc     9000

atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga     9060

tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga     9120

aaagtgccac ctgac                                                      9135


