                         SEQUENCE LISTING

<110>  EURO-CELTIQUE S.A.
 
<120>  HUMANIZED ANTIBODIES TARGETING HUMAN TISSUE FACTOR

<130>  1861.427PC01/JMC/KRM

<150>  62/591,168
<151>  2017-11-27

<160>  36    

<170>  PatentIn version 3.5

<210>  1
<211>  915
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of full length human tissue factor with a 32 
       AA N terminal leader sequence and 9 AA C-terminal  RGS-His6 tag

<400>  1
atggagaccc ctgcctggcc ccgggtcccg cgccccgaga ccgccgtcgc tcggacgctc       60

ctgctcggct gggtcttcgc ccaggtggcc ggcgcttcag gcactacaaa tactgtggca      120

gcatataatt taacttggaa atcaactaat ttcaagacaa ttttggagtg ggaacccaaa      180

cccgtcaatc aagtctacac tgttcaaata agcactaagt caggagattg gaaaagcaaa      240

tgcttttaca caacagacac agagtgtgac ctcaccgacg agattgtgaa ggatgtgaag      300

cagacgtact tggcacgggt cttctcctac ccggcaggga atgtggagag caccggttct      360

gctggggagc ctctgtatga gaactcccca gagttcacac cttacctgga gacaaacctc      420

ggacagccaa caattcagag ttttgaacag gtgggaacaa aagtgaatgt gaccgtagaa      480

gatgaacgga ctttagtcag aaggaacaac actttcctaa gcctccggga tgtttttggc      540

aaggacttaa tttatacact ttattattgg aaatcttcaa gttcaggaaa gaaaacagcc      600

aaaacaaaca ctaatgagtt tttgattgat gtggataaag gagaaaacta ctgtttcagt      660

gttcaagcag tgattccctc ccgaacagtt aaccggaaga gtacagacag cccggtagag      720

tgtatgggcc aggagaaagg ggaattcaga gaaatattct acatcattgg agctgtggta      780

tttgtggtca tcatccttgt catcatcctg gctatatctc tacacaagtg tagaaaggca      840

ggagtggggc agagctggaa ggagaactcc ccactgaatg tttcaagagg atcccaccat      900

caccatcacc attaa                                                       915


<210>  2
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid  sequence of full length human tissue factor with a 32
       AA N terminal leader sequence and 9 AA C-terminal  RGS-His6 tag

<400>  2

Met Glu Thr Pro Ala Trp Pro Arg Val Pro Arg Pro Glu Thr Ala Val 
1               5                   10                  15      


Ala Arg Thr Leu Leu Leu Gly Trp Val Phe Ala Gln Val Ala Gly Ala 
            20                  25                  30          


Ser Gly Thr Thr Asn Thr Val Ala Ala Tyr Asn Leu Thr Trp Lys Ser 
        35                  40                  45              


Thr Asn Phe Lys Thr Ile Leu Glu Trp Glu Pro Lys Pro Val Asn Gln 
    50                  55                  60                  


Val Tyr Thr Val Gln Ile Ser Thr Lys Ser Gly Asp Trp Lys Ser Lys 
65                  70                  75                  80  


Cys Phe Tyr Thr Thr Asp Thr Glu Cys Asp Leu Thr Asp Glu Ile Val 
                85                  90                  95      


Lys Asp Val Lys Gln Thr Tyr Leu Ala Arg Val Phe Ser Tyr Pro Ala 
            100                 105                 110         


Gly Asn Val Glu Ser Thr Gly Ser Ala Gly Glu Pro Leu Tyr Glu Asn 
        115                 120                 125             


Ser Pro Glu Phe Thr Pro Tyr Leu Glu Thr Asn Leu Gly Gln Pro Thr 
    130                 135                 140                 


Ile Gln Ser Phe Glu Gln Val Gly Thr Lys Val Asn Val Thr Val Glu 
145                 150                 155                 160 


Asp Glu Arg Thr Leu Val Arg Arg Asn Asn Thr Phe Leu Ser Leu Arg 
                165                 170                 175     


Asp Val Phe Gly Lys Asp Leu Ile Tyr Thr Leu Tyr Tyr Trp Lys Ser 
            180                 185                 190         


Ser Ser Ser Gly Lys Lys Thr Ala Lys Thr Asn Thr Asn Glu Phe Leu 
        195                 200                 205             


Ile Asp Val Asp Lys Gly Glu Asn Tyr Cys Phe Ser Val Gln Ala Val 
    210                 215                 220                 


Ile Pro Ser Arg Thr Val Asn Arg Lys Ser Thr Asp Ser Pro Val Glu 
225                 230                 235                 240 


Cys Met Gly Gln Glu Lys Gly Glu Phe Arg Glu Ile Phe Tyr Ile Ile 
                245                 250                 255     


Gly Ala Val Val Phe Val Val Ile Ile Leu Val Ile Ile Leu Ala Ile 
            260                 265                 270         


Ser Leu His Lys Cys Arg Lys Ala Gly Val Gly Gln Ser Trp Lys Glu 
        275                 280                 285             


Asn Ser Pro Leu Asn Val Ser Arg Gly Ser His His His His His His 
    290                 295                 300                 


<210>  3
<211>  783
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the extracellular domain of human tissue 
       factor with a 32 amino acid N-terminal leader sequence and a 9 
       amino acid C-terminal RGS-His6 tag sequence

<400>  3
atggagaccc ctgcctggcc ccgggtcccg cgccccgaga ccgccgtcgc tcggacgctc       60

ctgctcggct gggtcttcgc ccaggtggcc ggcgcttcag gcactacaaa tactgtggca      120

gcatataatt taacttggaa atcaactaat ttcaagacaa ttttggagtg ggaacccaaa      180

cccgtcaatc aagtctacac tgttcaaata agcactaagt caggagattg gaaaagcaaa      240

tgcttttaca caacagacac agagtgtgac ctcaccgacg agattgtgaa ggatgtgaag      300

cagacgtact tggcacgggt cttctcctac ccggcaggga atgtggagag caccggttct      360

gctggggagc ctctgtatga gaactcccca gagttcacac cttacctgga gacaaacctc      420

ggacagccaa caattcagag ttttgaacag gtgggaacaa aagtgaatgt gaccgtagaa      480

gatgaacgga ctttagtcag aaggaacaac actttcctaa gcctccggga tgtttttggc      540

aaggacttaa tttatacact ttattattgg aaatcttcaa gttcaggaaa gaaaacagcc      600

aaaacaaaca ctaatgagtt tttgattgat gtggataaag gagaaaacta ctgtttcagt      660

gttcaagcag tgattccctc ccgaacagtt aaccggaaga gtacagacag cccggtagag      720

tgtatgggcc aggagaaagg ggaattcaga gaaagaggat cccaccatca ccatcaccat      780

taa                                                                    783


<210>  4
<211>  260
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of the extracellular domain of human tissue 
       factor with a 32 amino acid N-terminal leader sequence and a 9 
       amino acid C-terminal RGS-His6 tag sequence.

<400>  4

Met Glu Thr Pro Ala Trp Pro Arg Val Pro Arg Pro Glu Thr Ala Val 
1               5                   10                  15      


Ala Arg Thr Leu Leu Leu Gly Trp Val Phe Ala Gln Val Ala Gly Ala 
            20                  25                  30          


Ser Gly Thr Thr Asn Thr Val Ala Ala Tyr Asn Leu Thr Trp Lys Ser 
        35                  40                  45              


Thr Asn Phe Lys Thr Ile Leu Glu Trp Glu Pro Lys Pro Val Asn Gln 
    50                  55                  60                  


Val Tyr Thr Val Gln Ile Ser Thr Lys Ser Gly Asp Trp Lys Ser Lys 
65                  70                  75                  80  


Cys Phe Tyr Thr Thr Asp Thr Glu Cys Asp Leu Thr Asp Glu Ile Val 
                85                  90                  95      


Lys Asp Val Lys Gln Thr Tyr Leu Ala Arg Val Phe Ser Tyr Pro Ala 
            100                 105                 110         


Gly Asn Val Glu Ser Thr Gly Ser Ala Gly Glu Pro Leu Tyr Glu Asn 
        115                 120                 125             


Ser Pro Glu Phe Thr Pro Tyr Leu Glu Thr Asn Leu Gly Gln Pro Thr 
    130                 135                 140                 


Ile Gln Ser Phe Glu Gln Val Gly Thr Lys Val Asn Val Thr Val Glu 
145                 150                 155                 160 


Asp Glu Arg Thr Leu Val Arg Arg Asn Asn Thr Phe Leu Ser Leu Arg 
                165                 170                 175     


Asp Val Phe Gly Lys Asp Leu Ile Tyr Thr Leu Tyr Tyr Trp Lys Ser 
            180                 185                 190         


Ser Ser Ser Gly Lys Lys Thr Ala Lys Thr Asn Thr Asn Glu Phe Leu 
        195                 200                 205             


Ile Asp Val Asp Lys Gly Glu Asn Tyr Cys Phe Ser Val Gln Ala Val 
    210                 215                 220                 


Ile Pro Ser Arg Thr Val Asn Arg Lys Ser Thr Asp Ser Pro Val Glu 
225                 230                 235                 240 


Cys Met Gly Gln Glu Lys Gly Glu Phe Arg Glu Arg Gly Ser His His 
                245                 250                 255     


His His His His 
            260 


<210>  5
<211>  363
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of the heavy chain variable region of murine 
       antibody TF278

<400>  5
gaggtccagc tgcagcaatc tggagctgag ctgatgaagc ctggggcctc agtgaagata       60

tcctgcaagg ctactggcta cacattcagt agctactgga tagagtgggt aaagcagagg      120

cctggacatg gccttgagtg gattggagag attttacctg gaagtgctag tactaagtac      180

aatgagaagt tcaagggcaa ggccacattc actgcagata catcctccaa cacagcctac      240

atgcaactca gcagcctgac atctgaggac tctgccgtct attactgtgc aagagattat      300

tactacggta gtagctacgg gtttgcttac tggggccaag ggactctggt cactgtctcg      360

agt                                                                    363


<210>  6
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid  sequence of the heavy chain variable region of murine
       antibody TF278

<400>  6

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


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


Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
        35                  40                  45              


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


Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  7
<211>  330
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of the light chain variable region of murine 
       antibody TF278

<400>  7
caggctgttg tgactcagga atctgcactc accacatcac ctggtgaaac agtcacactc       60

acttgtcgct caagtactgg ggctgttaca actagtaact atgccaactg ggtccaagaa      120

aaaccagatc atttattcac tggcctaata ggtggtacca acaaccgagg tccaggtgtt      180

cctgccagat tctcaggctc cctgattgga gacaaggctg ccctcaccat cacaggggca      240

cagactgagg atgaggcagt atatttctgt gctctatggt acagcaacca ttgggtgttc      300

ggtggaggaa ccaaactgac tgtcctaggt                                       330


<210>  8
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of the light chain variable region of 
       murine antibody TF278

<400>  8

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


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


Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Asp His Leu Phe Thr Gly 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Asn Arg Gly Pro Gly Val Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Ile Gly Asp Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  


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


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  9
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of the heavy chain variable region VH6 of 
       humanized TF antibody B278

<400>  9

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


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


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


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


Lys Gly Arg Val Thr Phe Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  10
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of heavy chain variable region VH4 of 
       humanized TF antibody B278

<400>  10

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


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


Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


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


Lys Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  


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


Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  11
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of heavy chain variable region VH5 of 
       humanized TF antibody B278

<400>  11

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


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


Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


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


Lys Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asn Thr Val Tyr 
65                  70                  75                  80  


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


Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  12
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of light chain variable region VL7 of 
       humanized TF antibody B278

<400>  12

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


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


Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Lys Gly 
        35                  40                  45              


Leu Ile Ser Gly Thr Asn Asn Arg Gly Pro Trp Thr Thr Ala Arg Phe 
    50                  55                  60                  


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


His Thr Glu Asp Glu Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  13
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of light chain variable region VL3 of 
       humanized TF antibody B278

<400>  13

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


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


Asn Tyr Ala Asn Trp Ile Gln Gln Lys Pro Gly Gln Gly Pro Lys Thr 
        35                  40                  45              


Leu Ile Ser Gly Thr Asn Asn Arg Gly Pro Trp Thr Thr Ala Arg Phe 
    50                  55                  60                  


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


His Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr His Leu Thr Val Gln Gly 
            100                 105                 110 


<210>  14
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of light chain variable region VL5 of humanized TF antibody B278

<400>  14

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


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


Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Thr Pro Thr Ser 
        35                  40                  45              


Leu Ile Ser Gly Thr Asn Asn Arg Gly Pro Trp Thr Pro Ala Arg Phe 
    50                  55                  60                  


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


His Ala Glu Asp Glu Ala Asp Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  15
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of light chain variable region VL6 of 
       humanized TF antibody B278

<400>  15

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


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


Asn Tyr Ala Asn Trp Val Gln Glu Lys Pro Gly His Gly Phe Lys Gly 
        35                  40                  45              


Leu Ile Ser Gly Thr Asn Asn Arg Gly Pro Trp Thr Thr Ala Arg Phe 
    50                  55                  60                  


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


His Ala Glu Asp Glu Ala Asp Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  16
<211>  110
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of light chain variable region VL8 of 
       humanized TF antibody B278

<400>  16

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


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


Asn Tyr Ala Asn Trp Val Gln Gln His Pro Gly Thr Val Pro Lys Pro 
        35                  40                  45              


Met Ile Tyr Gly Thr Asn Asn Arg Gly Pro Gly Val Pro Asp Arg Phe 
    50                  55                  60                  


Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Met Thr Ile Ser Gly Leu 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  17
<211>  451
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of full length heavy chain HC6

<400>  17

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


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


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


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


Lys Gly Arg Val Thr Phe Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


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


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


Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
        195                 200                 205             


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


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


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


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


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


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


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


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


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


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


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


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


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


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


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


Pro Gly Lys 
    450     


<210>  18
<211>  215
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino acid sequence of full length light chain LC7

<400>  18

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


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


Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Leu Pro Lys Gly 
        35                  40                  45              


Leu Ile Ser Gly Thr Asn Asn Arg Gly Pro Trp Thr Thr Ala Arg Phe 
    50                  55                  60                  


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


His Thr Glu Asp Glu Ala Val Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro 
            100                 105                 110         


Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu 
        115                 120                 125             


Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro 
    130                 135                 140                 


Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala 
145                 150                 155                 160 


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


Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg 
            180                 185                 190         


Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 
        195                 200                 205             


Val Ala Pro Thr Glu Cys Ser 
    210                 215 


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

<220>
<223>  VH-CDR1

<400>  19

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


<210>  20
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VH-CDR2

<400>  20

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


Gly 
    


<210>  21
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VH-CDR3

<400>  21

Ala Arg Asp Tyr Tyr Tyr Gly Ser Ser Tyr Gly Phe Ala Tyr 
1               5                   10                  


<210>  22
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VL-CDR1

<400>  22

Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
1               5                   10                  


<210>  23
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VL-CDR2

<400>  23

Gly Thr Asn Asn Arg Gly Pro 
1               5           


<210>  24
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VL-CDR3

<400>  24

Ala Leu Trp Tyr Ser Asn His Trp Val 
1               5                   


<210>  25
<211>  363
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of heavy chain variable region of humanized 
       TF antibody B278

<400>  25
gaggtccagc tgcaacagtc gggagcagag gtgatgaagc ccggagcctc agtgaagatt       60

agctgcaaag cctcgggata cactttctcg tcatactgga ttgaatgggt caaacaggcc      120

cccggccaag gactggagtg gattggcgaa atccttcctg ggagcgcctc gaccaagtac      180

aacgagaagt tcaagggacg cgtgacattc accgccgata ccagcaccaa cactgcctac      240

atggagctta gctcattgcg gtccgaggat accgctgtgt actactgtgc gcgggactac      300

tattacggct cctcatacgg cttcgcatac tggggacagg gtaccttggt cacggtgtcc      360

tcc                                                                    363


<210>  26
<211>  330
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of light chain variable region of humanized 
       TF antibody B278

<400>  26
caggctgtgg tcactcagga gccttcgctg actgtcagcc cgggcggtac cgtgaccctg       60

acctgtcgct cctcaactgg agcagtgacc acctccaact acgcgaactg ggtgcagcag      120

aaacccggcc aacttcctaa gggactgatc tccggcacta acaacagggg accttggacc      180

accgcccggt tctccggttc catccttggg gacaaggcgg tgctgacact gtggggggcc      240

cacacggagg acgaggccgt ctactactgc gcgctctggt actccaacca ttgggtgttt      300

ggcggaggca ctaagttgac cgtgctgggc                                       330


<210>  27
<211>  1356
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of full length heavy chain of humanized TF 
       antibody

<400>  27
gaggtccagc tgcaacagtc gggagcagag gtgatgaagc ccggagcctc agtgaagatt       60

agctgcaaag cctcgggata cactttctcg tcatactgga ttgaatgggt caaacaggcc      120

cccggccaag gactggagtg gattggcgaa atccttcctg ggagcgcctc gaccaagtac      180

aacgagaagt tcaagggacg cgtgacattc accgccgata ccagcaccaa cactgcctac      240

atggagctta gctcattgcg gtccgaggat accgctgtgt actactgtgc gcgggactac      300

tattacggct cctcatacgg cttcgcatac tggggtcagg gaaccttggt cacggtgtcc      360

tccgcgtcca ccaagggtcc ctccgtgttc cctctcgcgc cgtcctcaaa gtctacctcc      420

ggtggaactg ccgcgctcgg ttgtctcgtg aaggactact tcccggagcc tgtgactgtc      480

tcctggaact ccggggccct caccagcgga gtgcacactt tccccgccgt gctgcaatcc      540

tccggcctgt acagcctgtc ctccgtcgtg actgtgccta gctcctccct gggaacccag      600

acctacatct gcaacgtgaa ccacaagccc tccaacacca aggtcgacaa gaaggtcgaa      660

ccgaagtcgt gcgacaagac tcatacgtgc cctccttgcc cggccccgga actgctggga      720

ggcccatccg tgttcctgtt cccacccaag cctaaggata ccctgatgat cagcagaaca      780

ccggaagtga cctgtgtggt ggtggacgtc agccacgaag atcccgaggt caagttcaat      840

tggtacgtgg acggggtgga ggtgcacaac gcaaagacca agccccggga ggaacagtac      900

aactccacct atcgcgtggt gtcggtgctg acggtgctgc accaggactg gttgaacgga      960

aaggagtata agtgcaaagt gtcgaacaag gccctgcccg ctcctatcga aaagaccatc     1020

tccaaggcca agggccagcc gcgggaaccc caggtctaca ctctcccacc gagccgcgac     1080

gaactgacta agaatcaagt gtcgctgact tgcctcgtca agggcttcta cccgtccgac     1140

atcgccgtgg aatgggagag caacggccag ccggaaaaca actacaagac cacccctccc     1200

gtgctggatt ccgacgggtc cttcttcctg tactcaaaac tgaccgtgga taagtccaga     1260

tggcagcagg gcaatgtctt ttcatgctcc gtgatgcacg aggctctgca taaccactac     1320

acccagaagt cgctgtccct gtccccgggg aagtga                               1356


<210>  28
<211>  648
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of full length light chain of humanized TF 
       antibody

<400>  28
caggctgtgg tcactcagga gccttcgctg actgtcagcc cgggtggcac cgtgaccctg       60

acctgtcgct cctcaactgg agcagtgacc acctccaact acgcgaactg ggtgcagcag      120

aaacccggcc aacttcctaa gggactgatc tccggcacta acaacagggg accttggacc      180

accgcccggt tctccggttc catccttggg gacaaggcgg tgctgacact gtggggggcc      240

cacacggagg acgaggccgt ctactactgc gcgctctggt actccaacca ttgggtgttt      300

ggcggaggca ctaagttgac cgtgctgggc cagcctaagg ccgcaccatc ggtgaccctg      360

ttcccgccga gctcggaaga actccaggcc aacaaggcca ctctggtctg cctgatttcc      420

gacttctatc ccggtgctgt gaccgtggct tggaaggccg atagctcgcc cgtgaaggcc      480

ggagtggaaa ccaccacccc gtccaaacag tccaacaata agtacgccgc ctcctcctac      540

ttgagcctca cgcccgagca gtggaagtct caccgctcat actcctgcca agtcacccac      600

gaagggagca ctgtggaaaa gaccgtggca cccactgagt gctcgtga                   648


<210>  29
<211>  57
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  29
atgggatgga ctctcgtgtt cctttttctc ctctctgtca ctgccggggt gcattcg          57


<210>  30
<211>  19
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  30

Met Gly Trp Thr Leu Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly 
1               5                   10                  15      


Val His Ser 
            


<210>  31
<211>  60
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  31
atggtgtcaa gcgcgcagtt tctgggactg ctcctgctgt gtttccaagg aaccagatgc       60


<210>  32
<211>  20
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  32

Met Val Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln 
1               5                   10                  15      


Gly Thr Arg Cys 
            20  


<210>  33
<211>  60
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  33
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg atctactggc       60


<210>  34
<211>  20
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic

<400>  34

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


Gly Ser Thr Gly 
            20  


<210>  35
<211>  363
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of heavy chain variable region of humanized 
       TF antibody B278

<400>  35
gaggtccagc tgcaacagtc gggagcagag gtgatgaagc ccggagcctc agtgaagatt       60

agctgcaaag cctcgggata cactttctcg tcatactgga ttgaatgggt caaacaggcc      120

cccggccaag gactggagtg gattggcgaa atccttcctg ggagcgcctc gaccaagtac      180

aacgagaagt tcaagggacg cgtgacattc accgccgata ccagcaccaa cactgcctac      240

atggagctta gctcattgcg gtccgaggat accgctgtgt actactgtgc gcgggactac      300

tattacggct cctcatacgg cttcgcatac tggggtcagg gaaccttggt cacggtgtcc      360

tcc                                                                    363


<210>  36
<211>  330
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleotide sequence of light chain variable region of humanized 
       TF antibody B278

<400>  36
caggctgtgg tcactcagga gccttcgctg actgtcagcc cgggtggcac cgtgaccctg       60

acctgtcgct cctcaactgg agcagtgacc acctccaact acgcgaactg ggtgcagcag      120

aaacccggcc aacttcctaa gggactgatc tccggcacta acaacagggg accttggacc      180

accgcccggt tctccggttc catccttggg gacaaggcgg tgctgacact gtggggggcc      240

cacacggagg acgaggccgt ctactactgc gcgctctggt actccaacca ttgggtgttt      300

ggcggaggca ctaagttgac cgtgctgggc                                       330


