                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Treatment with a humanized anti-EGFR IgG1 antibody and Irinotecan

<130>  26054

<150>  EP 09156844.4
<151>  2009-03-31

<160>  40    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Kabat

<400>  1

Asp Tyr Lys Ile His 
1               5   


<210>  2
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Kabat

<400>  2

Asp Tyr Ala Ile Ser 
1               5   


<210>  3
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Kabat

<400>  3

Asp Tyr Tyr Met His 
1               5   


<210>  4
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Kabat

<400>  4

Asp Tyr Lys Ile Ser 
1               5   


<210>  5
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Chothia

<400>  5

Gly Phe Thr Phe Thr Asp Tyr 
1               5           


<210>  6
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 Chothia

<400>  6

Gly Tyr Thr Phe Thr Asp Tyr 
1               5           


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

<220>
<223>  Heavy Chain CDR1 Chothia

<400>  7

Gly Tyr Ser Phe Thr Asp Tyr 
1               5           


<210>  8
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 AbM

<400>  8

Gly Phe Thr Phe Thr Asp Tyr Lys Ile His 
1               5                   10  


<210>  9
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 AbM

<400>  9

Gly Phe Thr Phe Thr Asp Tyr Ala Ile Ser 
1               5                   10  


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

<220>
<223>  Heavy Chain CDR1 AbM

<400>  10

Gly Phe Thr Phe Thr Asp Tyr Tyr Met His 
1               5                   10  


<210>  11
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 AbM

<400>  11

Gly Tyr Thr Phe Thr Asp Tyr Tyr Met His 
1               5                   10  


<210>  12
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 AbM

<400>  12

Gly Tyr Ser Phe Thr Asp Tyr Lys Ile His 
1               5                   10  


<210>  13
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR1 AbM

<400>  13

Gly Phe Thr Phe Thr Asp Tyr Lys Ile Ser 
1               5                   10  


<210>  14
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  14

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


Ser 
    


<210>  15
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  15

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


Gly 
    


<210>  16
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  16

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


Gly 
    


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

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  17

Trp Ile Asn Pro Asn Ser Gly Tyr Ser Thr Tyr Ala Gln Lys Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  18
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  18

Trp Ile Asn Pro Asn Ser Gly Tyr Ser Thr Tyr Ser Pro Ser Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  19
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  19

Trp Ile Asn Pro Asn Ser Gly Tyr Ser Thr Tyr Asn Glu Lys Phe Gln 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  20

Tyr Phe Asn Pro Asn Ser Gly Tyr Ser Asn Tyr Ala Gln Lys Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  21
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  21

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


Gly 
    


<210>  22
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Kabat

<400>  22

Tyr Phe Asn Pro Asn Ser Gly Tyr Ser Thr Tyr Ser Pro Ser Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  23
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Chothia

<400>  23

Asn Pro Asn Ser Gly Tyr Ser Thr 
1               5               


<210>  24
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Chothia

<400>  24

Asn Pro Asn Ser Gly Tyr Ser Asn 
1               5               


<210>  25
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 Chothia

<400>  25

Asn Pro Asn Ser Gly Tyr Ala Thr 
1               5               


<210>  26
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 AbM

<400>  26

Tyr Phe Asn Pro Asn Ser Gly Tyr Ser Thr 
1               5                   10  


<210>  27
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 AbM

<400>  27

Gly Ile Asn Pro Asn Ser Gly Tyr Ser Thr 
1               5                   10  


<210>  28
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 AbM

<400>  28

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


<210>  29
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 AbM

<400>  29

Tyr Phe Asn Pro Asn Ser Gly Tyr Ser Asn 
1               5                   10  


<210>  30
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR2 AbM

<400>  30

Tyr Phe Asn Pro Asn Ser Gly Tyr Ala Thr 
1               5                   10  


<210>  31
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy Chain CDR3 Kabat Chothia AbM

<400>  31

Leu Ser Pro Gly Gly Tyr Tyr Val Met Asp Ala 
1               5                   10      


<210>  32
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light Chain CDR1 Kabat

<400>  32

Lys Ala Ser Gln Asn Ile Asn Asn Tyr Leu Asn 
1               5                   10      


<210>  33
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light Chain CDR1 Kabat

<400>  33

Arg Ala Ser Gln Gly Ile Asn Asn Tyr Leu Asn 
1               5                   10      


<210>  34
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light Chain CDR2 Kabat

<400>  34

Asn Thr Asn Asn Leu Gln Thr 
1               5           


<210>  35
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light Chain CDR3 Kabat

<400>  35

Leu Gln His Asn Ser Phe Pro Thr 
1               5               


<210>  36
<211>  120
<212>  PRT
<213>  Rattus norvegicus


<220>
<221>  MISC_FEATURE
<223>  ICR62 VH

<400>  36

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


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


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


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


Lys Ser Lys Ala Thr Leu Thr Ala Asp Lys Ser Thr Asp Thr Ala Tyr 
65                  70                  75                  80  


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


Thr Arg Leu Ser Pro Gly Gly Tyr Tyr Val Met Asp Ala Trp Gly Gln 
            100                 105                 110         


Gly Ala Ser Val Thr Val Ser Ser 
        115                 120 


<210>  37
<211>  108
<212>  PRT
<213>  Rattus norvegicus


<220>
<221>  MISC_FEATURE
<223>  ICR62 VL

<400>  37

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


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


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


Tyr Asn Thr Asn Asn Leu Gln Thr Gly Ile 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 Phe Cys Leu Gln His Asn Ser Phe Pro Thr 
                85                  90                  95      


Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr 
            100                 105             


<210>  38
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  I-HHD VH construct

<400>  38

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


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


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


Gly Tyr Phe Asn Pro Asn Ser Gly Tyr Ser Thr Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser 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 Leu Ser Pro Gly Gly Tyr Tyr Val Met Asp Ala Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  39
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  I-KC VL construct

<400>  39

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 Gly Ile Asn Asn Tyr 
            20                  25                  30          


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


Tyr Asn Thr Asn Asn Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His Asn Ser Phe Pro Thr 
                85                  90                  95      


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


<210>  40
<211>  328
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Ig gamma-1 CH region

<400>  40

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
1               5                   10                  15      


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


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
        35                  40                  45              


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
    50                  55                  60                  


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


Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Ala 
                85                  90                  95      


Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
            100                 105                 110         


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
        115                 120                 125             


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
    130                 135                 140                 


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


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
                165                 170                 175     


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
            180                 185                 190         


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
        195                 200                 205             


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
    210                 215                 220                 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
225                 230                 235                 240 


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
                245                 250                 255     


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
            260                 265                 270         


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
        275                 280                 285             


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
    290                 295                 300                 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
305                 310                 315                 320 


Ser Leu Ser Leu Ser Pro Gly Lys 
                325             


