                         SEQUENCE LISTING

<110>  National Research Council of Canada
 
<120>  HUMANIZED ANTI-EGFRVIII ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS 
       THEREOF

<130>  2022-063-01

<140>  PCT/IB2021/058954
<141>  2021-09-29

<160>  26    

<170>  PatentIn version 3.5

<210>  1
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine 4E11 VH region

<400>  1

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


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


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


Met Gly Tyr Ile Gly Tyr Asn Gly Arg Thr Ser Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ala 
        115     


<210>  2
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine 4E11 VL region

<400>  2

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


Asp Thr Val Ser Ile Thr Cys His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


Ile Gly Trp Leu Leu Gln Lys Pro Gly Lys Ser Phe Lys Gly Leu Ile 
        35                  40                  45              


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser 
65                  70                  75                  80  


Glu Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Gln Phe Pro Tyr 
                85                  90                  95      


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


<210>  3
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Consensus humanized 4E11 VH region


<220>
<221>  SITE
<222>  (49)..(49)
<223>  X at position 49 is I or M

<220>
<221>  SITE
<222>  (68)..(68)
<223>  X at position 68 is V or I

<220>
<221>  SITE
<222>  (72)..(72)
<223>  X at position 72 is V or R

<400>  3

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


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


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


Xaa Gly Tyr Ile Gly Tyr Asn Gly Arg Thr Ser Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  4
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Consensus humanized 4E11 VL region


<220>
<221>  SITE
<222>  (36)..(36)
<223>  X at position 36 is Y or L

<220>
<221>  SITE
<222>  (44)..(44)
<223>  X at position 44 is P or F

<220>
<221>  SITE
<222>  (46)..(46)
<223>  X at position 46 is L or G

<400>  4

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


Ile Gly Trp Xaa Gln Gln Lys Pro Gly Lys Ala Xaa Lys Xaa Leu Ile 
        35                  40                  45              


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  5
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VH region variant 1

<400>  5

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


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


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


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


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  6
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VH region variant 2

<400>  6

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


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


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


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


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  7
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VH region variant 3

<400>  7

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


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


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


Met Gly Tyr Ile Gly Tyr Asn Gly Arg Thr Ser Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  8
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VL region variant 1

<400>  8

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


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


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  9
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VL region variant 2

<400>  9

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


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


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  10
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 VL region variant 3

<400>  10

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


Ile Gly Trp Leu Gln Gln Lys Pro Gly Lys Ala Phe Lys Gly Leu Ile 
        35                  40                  45              


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  11
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 4E11 heavy chain on human IgG4(S228P) background

<400>  11

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


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


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


Met Gly Tyr Ile Gly Tyr Asn Gly Arg Thr Ser Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


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


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


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440         


<210>  12
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 4E11 light chain on human kappa background

<400>  12

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


Asp Thr Val Ser Ile Thr Cys His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


Ile Gly Trp Leu Leu Gln Lys Pro Gly Lys Ser Phe Lys Gly Leu Ile 
        35                  40                  45              


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser 
65                  70                  75                  80  


Glu Asp Phe Ala Asp Tyr Tyr Cys Val Gln Tyr Ala Gln Phe Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  13
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 heavy chain variant 1 on human IgG4(S228P) 
       background

<400>  13

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


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


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


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


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


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


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


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440         


<210>  14
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 heavy chain variant 2 on human IgG4(S228P) 
       background

<400>  14

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


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


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


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


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


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


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


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440         


<210>  15
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 heavy chain variant 3 on human IgG4(S228P) 
       background

<400>  15

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


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


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


Met Gly Tyr Ile Gly Tyr Asn Gly Arg Thr Ser Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Leu Gly Arg Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


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


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


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440         


<210>  16
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 light chain variant 1 on human kappa background

<400>  16

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


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


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  17
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 light chain variant 2 on human kappa background

<400>  17

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


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


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  18
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 4E11 light chain variant 3 on human kappa background

<400>  18

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 His Ala Ser Gln Gly Ile Asn Ser Asn 
            20                  25                  30          


Ile Gly Trp Leu Gln Gln Lys Pro Gly Lys Ala Phe Lys Gly Leu Ile 
        35                  40                  45              


Tyr His Gly Thr Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


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

<220>
<223>  Signal peptide on heavy chain (exemplary)

<400>  19

Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 
1               5                   10                  15      


Thr His Ala 
            


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

<220>
<223>  Signal peptide on light chain (exemplary)

<400>  20

Met Val Leu Gln Thr Gln Val Phe Ile Ser Leu Leu Leu Trp Ile Ser 
1               5                   10                  15      


Gly Ala Tyr Gly 
            20  


<210>  21
<211>  1383
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 heavy chain variant 1 on human 
       IgG4(S228P) background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(57)
<223>  Exemplary signal peptide sequence

<400>  21
atggactgga cctggaggat cctgttcctg gtggccgccg ccaccggcac ccacgcccag       60

gtgcagctgc aggagtccgg ccccggcctg gtgaagccct cccagaccct gtccctgacc      120

tgcaccgtgt ccggctactc catcacctcc gactacgcct ggaactggat caggcagccc      180

cccggcaagg gcctggagtg gatcggctac atcggctaca acggcaggac ctcctacaac      240

ccctccctga agtccagggt gaccatctcc gtggacacct ccaagaacca gttctccctg      300

aagctgtcct ccgtgaccgc cgccgacacc gccgtgtact actgcgccag gctgggcagg      360

ggcttcgcct actggggcca gggcaccctg gtgaccgtgt cctccgcctc caccaagggc      420

ccctccgtgt tccccctggc cccctgctcc aggtccacct ccgagtccac cgccgccctg      480

ggctgcctgg tgaaggacta cttccccgag cccgtgaccg tgtcctggaa ctccggcgcc      540

ctgacctccg gcgtgcacac cttccccgcc gtgctgcagt cctccggcct gtactccctg      600

tcctccgtgg tgaccgtgcc ctcctcctcc ctgggcacca agacctacac ctgcaacgtg      660

gaccacaagc cctccaacac caaggtggac aagagggtgg agtccaagta cggccccccc      720

tgccccccct gccccgcccc cgagttcctg ggcggcccct ccgtgttcct gttccccccc      780

aagcccaagg acaccctgat gatctccagg acccccgagg tgacctgcgt ggtggtggac      840

gtgtcccagg aggaccccga ggtgcagttc aactggtacg tggacggcgt ggaggtgcac      900

aacgccaaga ccaagcccag ggaggagcag ttcaactcca cctacagggt ggtgtccgtg      960

ctgaccgtgc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtgtccaac     1020

aagggcctgc cctcctccat cgagaagacc atctccaagg ccaagggcca gcccagggag     1080

ccccaggtgt acaccctgcc cccctcccag gaggagatga ccaagaacca ggtgtccctg     1140

acctgcctgg tgaagggctt ctacccctcc gacatcgccg tggagtggga gtccaacggc     1200

cagcccgaga acaactacaa gaccaccccc cccgtgctgg actccgacgg ctccttcttc     1260

ctgtactcca ggctgaccgt ggacaagtcc aggtggcagg agggcaacgt gttctcctgc     1320

tccgtgatgc acgaggccct gcacaaccac tacacccaga agtccctgtc cctgtccctg     1380

ggc                                                                   1383


<210>  22
<211>  1383
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 heavy chain variant 2 on human 
       IgG4(S228P) background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(57)
<223>  Exemplary signal peptide sequence

<400>  22
atggactgga cctggaggat cctgttcctg gtggccgccg ccaccggcac ccacgcccag       60

gtgcagctgc aggagtccgg ccccggcctg gtgaagccct cccagaccct gtccctgacc      120

tgcaccgtgt ccggctactc catcacctcc gactacgcct ggaactggat caggcagccc      180

cccggcaagg gcctggagtg gatcggctac atcggctaca acggcaggac ctcctacaac      240

ccctccctga agtccagggt gaccatctcc agggacacct ccaagaacca gttctccctg      300

aagctgtcct ccgtgaccgc cgccgacacc gccgtgtact actgcgccag gctgggcagg      360

ggcttcgcct actggggcca gggcaccctg gtgaccgtgt cctccgcctc caccaagggc      420

ccctccgtgt tccccctggc cccctgctcc aggtccacct ccgagtccac cgccgccctg      480

ggctgcctgg tgaaggacta cttccccgag cccgtgaccg tgtcctggaa ctccggcgcc      540

ctgacctccg gcgtgcacac cttccccgcc gtgctgcagt cctccggcct gtactccctg      600

tcctccgtgg tgaccgtgcc ctcctcctcc ctgggcacca agacctacac ctgcaacgtg      660

gaccacaagc cctccaacac caaggtggac aagagggtgg agtccaagta cggccccccc      720

tgccccccct gccccgcccc cgagttcctg ggcggcccct ccgtgttcct gttccccccc      780

aagcccaagg acaccctgat gatctccagg acccccgagg tgacctgcgt ggtggtggac      840

gtgtcccagg aggaccccga ggtgcagttc aactggtacg tggacggcgt ggaggtgcac      900

aacgccaaga ccaagcccag ggaggagcag ttcaactcca cctacagggt ggtgtccgtg      960

ctgaccgtgc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtgtccaac     1020

aagggcctgc cctcctccat cgagaagacc atctccaagg ccaagggcca gcccagggag     1080

ccccaggtgt acaccctgcc cccctcccag gaggagatga ccaagaacca ggtgtccctg     1140

acctgcctgg tgaagggctt ctacccctcc gacatcgccg tggagtggga gtccaacggc     1200

cagcccgaga acaactacaa gaccaccccc cccgtgctgg actccgacgg ctccttcttc     1260

ctgtactcca ggctgaccgt ggacaagtcc aggtggcagg agggcaacgt gttctcctgc     1320

tccgtgatgc acgaggccct gcacaaccac tacacccaga agtccctgtc cctgtccctg     1380

ggc                                                                   1383


<210>  23
<211>  1383
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 heavy chain variant 3 on human 
       IgG4(S228P) background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(57)
<223>  Exemplary signal peptide sequence

<400>  23
atggactgga cctggaggat cctgttcctg gtggccgccg ccaccggcac ccacgcccag       60

gtgcagctgc aggagtccgg ccccggcctg gtgaagccct cccagaccct gtccctgacc      120

tgcaccgtgt ccggctactc catcacctcc gactacgcct ggaactggat caggcagccc      180

cccggcaagg gcctggagtg gatgggctac atcggctaca acggcaggac ctcctacaac      240

ccctccctga agtccaggat caccatctcc agggacacct ccaagaacca gttctccctg      300

aagctgtcct ccgtgaccgc cgccgacacc gccgtgtact actgcgccag gctgggcagg      360

ggcttcgcct actggggcca gggcaccctg gtgaccgtgt cctccgcctc caccaagggc      420

ccctccgtgt tccccctggc cccctgctcc aggtccacct ccgagtccac cgccgccctg      480

ggctgcctgg tgaaggacta cttccccgag cccgtgaccg tgtcctggaa ctccggcgcc      540

ctgacctccg gcgtgcacac cttccccgcc gtgctgcagt cctccggcct gtactccctg      600

tcctccgtgg tgaccgtgcc ctcctcctcc ctgggcacca agacctacac ctgcaacgtg      660

gaccacaagc cctccaacac caaggtggac aagagggtgg agtccaagta cggccccccc      720

tgccccccct gccccgcccc cgagttcctg ggcggcccct ccgtgttcct gttccccccc      780

aagcccaagg acaccctgat gatctccagg acccccgagg tgacctgcgt ggtggtggac      840

gtgtcccagg aggaccccga ggtgcagttc aactggtacg tggacggcgt ggaggtgcac      900

aacgccaaga ccaagcccag ggaggagcag ttcaactcca cctacagggt ggtgtccgtg      960

ctgaccgtgc tgcaccagga ctggctgaac ggcaaggagt acaagtgcaa ggtgtccaac     1020

aagggcctgc cctcctccat cgagaagacc atctccaagg ccaagggcca gcccagggag     1080

ccccaggtgt acaccctgcc cccctcccag gaggagatga ccaagaacca ggtgtccctg     1140

acctgcctgg tgaagggctt ctacccctcc gacatcgccg tggagtggga gtccaacggc     1200

cagcccgaga acaactacaa gaccaccccc cccgtgctgg actccgacgg ctccttcttc     1260

ctgtactcca ggctgaccgt ggacaagtcc aggtggcagg agggcaacgt gttctcctgc     1320

tccgtgatgc acgaggccct gcacaaccac tacacccaga agtccctgtc cctgtccctg     1380

ggc                                                                   1383


<210>  24
<211>  702
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 light chain variant 1 on human 
       kappa background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(60)
<223>  Exemplary signal peptide sequence

<400>  24
atggtgctgc agacccaggt gttcatctcc ctgctgctgt ggatctccgg cgcctacggc       60

gacatccaga tgacccagtc cccctcctcc ctgtccgcct ccgtgggcga cagggtgacc      120

atcacctgcc acgcctccca gggcatcaac tccaacatcg gctggtacca gcagaagccc      180

ggcaaggccc ccaagctgct gatctaccac ggcaccaacc tggaggacgg cgtgccctcc      240

aggttctccg gctccggctc cggcaccgac tacaccctga ccatctcctc cctgcagccc      300

gaggacttcg ccacctacta ctgcgtgcag tacgcccagt tcccctacac cttcggccag      360

ggcaccaagc tggagatcaa gaggaccgtg gccgccccct ccgtgttcat cttccccccc      420

tccgacgagc agctgaagtc cggcaccgcc tccgtggtgt gcctgctgaa caacttctac      480

cccagggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagtccgg caactcccag      540

gagtccgtga ccgagcagga ctccaaggac tccacctact ccctgtcctc caccctgacc      600

ctgtccaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtgac ccaccagggc      660

ctgtcctccc ccgtgaccaa gtccttcaac aggggcgagt gc                         702


<210>  25
<211>  702
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 light chain variant 2 on human 
       kappa background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(60)
<223>  Exemplary signal peptide sequence

<400>  25
atggtgctgc agacccaggt gttcatctcc ctgctgctgt ggatctccgg cgcctacggc       60

gacatccaga tgacccagtc cccctcctcc ctgtccgcct ccgtgggcga cagggtgacc      120

atcacctgcc acgcctccca gggcatcaac tccaacatcg gctggctgca gcagaagccc      180

ggcaaggccc ccaagggcct gatctaccac ggcaccaacc tggaggacgg cgtgccctcc      240

aggttctccg gctccggctc cggcaccgac tacaccctga ccatctcctc cctgcagccc      300

gaggacttcg ccacctacta ctgcgtgcag tacgcccagt tcccctacac cttcggccag      360

ggcaccaagc tggagatcaa gaggaccgtg gccgccccct ccgtgttcat cttccccccc      420

tccgacgagc agctgaagtc cggcaccgcc tccgtggtgt gcctgctgaa caacttctac      480

cccagggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagtccgg caactcccag      540

gagtccgtga ccgagcagga ctccaaggac tccacctact ccctgtcctc caccctgacc      600

ctgtccaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtgac ccaccagggc      660

ctgtcctccc ccgtgaccaa gtccttcaac aggggcgagt gc                         702


<210>  26
<211>  702
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of humanized 4E11 light chain variant 3 on human 
       kappa background including an exemplary signal peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(60)
<223>  Exemplary signal peptide sequence

<400>  26
atggtgctgc agacccaggt gttcatctcc ctgctgctgt ggatctccgg cgcctacggc       60

gacatccaga tgacccagtc cccctcctcc ctgtccgcct ccgtgggcga cagggtgacc      120

atcacctgcc acgcctccca gggcatcaac tccaacatcg gctggctgca gcagaagccc      180

ggcaaggcct tcaagggcct gatctaccac ggcaccaacc tggaggacgg cgtgccctcc      240

aggttctccg gctccggctc cggcaccgac tacaccctga ccatctcctc cctgcagccc      300

gaggacttcg ccacctacta ctgcgtgcag tacgcccagt tcccctacac cttcggccag      360

ggcaccaagc tggagatcaa gaggaccgtg gccgccccct ccgtgttcat cttccccccc      420

tccgacgagc agctgaagtc cggcaccgcc tccgtggtgt gcctgctgaa caacttctac      480

cccagggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagtccgg caactcccag      540

gagtccgtga ccgagcagga ctccaaggac tccacctact ccctgtcctc caccctgacc      600

ctgtccaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtgac ccaccagggc      660

ctgtcctccc ccgtgaccaa gtccttcaac aggggcgagt gc                         702


