                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Method for making antibody Fc-region conjugates comprising at 
       least one binding entity that specifically binds to a target and 
       uses thereof

<130>  31068 WO

<150>  EP12173876.9
<151>  2012-06-27

<160>  74    

<170>  PatentIn version 3.5

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

<220>
<223>  sortase amino acid sequence tag


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X can be any amino acid residue

<400>  1

Leu Pro Xaa Thr Gly 
1               5   


<210>  2
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase amino acid sequence tag 2


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = G or GG or GGG

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<400>  2

Xaa Ser Leu Pro Xaa Thr Gly 
1               5           


<210>  3
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase amino acid sequence tag 3


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<400>  3

Gly Ser Leu Pro Xaa Thr Gly Gly Ser Gly Ser 
1               5                   10      


<210>  4
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase amino acid sequence tag 5


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = any amino acid residue except G

<220>
<221>  misc_feature
<222>  (6)..(6)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  X = any amino acid residue

<400>  4

Xaa Gly Ser Leu Pro Xaa Thr Gly Gly Ser Gly Ser 
1               5                   10          


<210>  5
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase amino acid sequence tag 5


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = G or GG or GGG

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  X = amino acid sequence tag

<400>  5

Xaa Ser Leu Pro Xaa Thr Gly Gly Ser Gly Ser Xaa 
1               5                   10          


<210>  6
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase amino acid sequence tag 6


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = any amino acid residue except G

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  X = amino acid sequence tag

<400>  6

Xaa Gly Ser Leu Pro Xaa Thr Gly Gly Ser Gly Ser Xaa 
1               5                   10              


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

<220>
<223>  hinge nucleophile


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = S or P

<400>  7

Gly Gly Cys Pro Xaa Cys 
1               5       


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

<220>
<223>  hinge nucleophile 2


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  X = S or P

<400>  8

Gly Gly His Thr Cys Pro Xaa Cys 
1               5               


<210>  9
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase product characteristic amino acid sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = G or GG or GGG

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<400>  9

Xaa Ser Leu Pro Xaa Thr Gly Gly 
1               5               


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

<220>
<223>  sortase product characteristic amino acid sequence 2


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = G or GG or GGG

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  X = S or P

<400>  10

Xaa Ser Leu Pro Xaa Thr Gly Gly Cys Pro Xaa Cys 
1               5                   10          


<210>  11
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase product characteristic amino acid sequence 3


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = any amino acid residue except G

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  X = S or P

<400>  11

Xaa Gly Ser Leu Pro Xaa Thr Gly Gly Cys Pro Xaa Cys 
1               5                   10              


<210>  12
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase product characteristic amino acid sequence 4


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = G or GG or GGG

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  X = S or P

<400>  12

Xaa Ser Leu Pro Xaa Thr Gly Gly His Thr Cys Pro Xaa Cys 
1               5                   10                  


<210>  13
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase product characteristic amino acid sequence 5


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X = any amino acid residue except G

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X = any amino acid residue

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  X = S or P

<400>  13

Xaa Gly Ser Leu Pro Xaa Thr Gly Gly His Thr Cys Pro Xaa Cys 
1               5                   10                  15  


<210>  14
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase tag example

<400>  14

Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His His His 
1               5                   10                  15  


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

<220>
<223>  sortase tag example 2

<400>  15

Gly Ser Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His His 
1               5                   10                  15      


His 
    


<210>  16
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sortase tag example 3

<400>  16

Gly Gly Gly Ser Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His 
1               5                   10                  15      


His His His 
            


<210>  17
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge nucleophile example

<400>  17

Gly Gly Cys Pro Pro Cys 
1               5       


<210>  18
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge nucleophile example 2

<400>  18

Gly Gly His Thr Cys Pro Pro Cys 
1               5               


<210>  19
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge nucleophile example 3

<400>  19

Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys 
1               5                   10          


<210>  20
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Arg-tag

<400>  20

Arg Arg Arg Arg Arg 
1               5   


<210>  21
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Arg-tag 2

<400>  21

Arg Arg Arg Arg Arg Arg 
1               5       


<210>  22
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  His-tag

<400>  22

His His His His His His 
1               5       


<210>  23
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  23

Lys Asp His Leu Ile His Asn Val His Lys Glu Phe His Ala His Ala 
1               5                   10                  15      


His Asn Lys 
            


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

<220>
<223>  amino acid tag

<400>  24

Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5               


<210>  25
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  25

Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr 
1               5                   10                  15      


Lys Asp Asp Asp Asp Lys 
            20          


<210>  26
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag#

<400>  26

Ala Trp Arg His Pro Gln Phe Gly Gly 
1               5                   


<210>  27
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  27

Trp Ser His Pro Gln Phe Glu Lys 
1               5               


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

<220>
<223>  amino acid tag

<400>  28

Met Asp Val Glu Ala Trp Leu Gly Ala Arg 
1               5                   10  


<210>  29
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  29

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


<210>  30
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  30

Met Asp Glu Lys Thr Thr Gly Trp Arg Gly Gly His Val Val Glu Gly 
1               5                   10                  15      


Leu Ala Gly Glu Leu Glu Gln Leu Arg Ala Arg Leu Glu His His Pro 
            20                  25                  30          


Gln Gly Gln Arg Glu Pro 
        35              


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

<220>
<223>  amino acid tag

<400>  31

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  32
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  32

Lys Glu Thr Ala Ala Ala Lys Phe Glu Arg Gln His Met Asp Ser 
1               5                   10                  15  


<210>  33
<211>  26
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  33

Lys Arg Arg Trp Lys Lys Asn Phe Ile Ala Val Ser Ala Ala Asn Arg 
1               5                   10                  15      


Phe Lys Lys Ile Ser Ser Ser Gly Ala Leu 
            20                  25      


<210>  34
<211>  47
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  amino acid tag

<400>  34

Pro Ala Thr Thr Thr Gly Ser Ser Pro Gly Pro Thr Gln Ser His Tyr 
1               5                   10                  15      


Gly Gln Cys Gly Gly Ile Gly Tyr Ser Gly Pro Thr Val Cys Ala Ser 
            20                  25                  30          


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


<210>  35
<211>  32
<212>  PRT
<213>  Butyrivibrio fibrisolvens

<400>  35

Met Asp Trp Asn Ala Asn Ile Ala Pro Gly Asn Ser Val Glu Phe Gly 
1               5                   10                  15      


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


<210>  36
<211>  51
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  chitin-binding-domain

<400>  36

Thr Asn Pro Gly Val Ser Ala Trp Gln Val Asn Thr Ala Tyr Thr Ala 
1               5                   10                  15      


Gly Gln Leu Val Thr Tyr Asn Gly Lys Thr Tyr Lys Cys Leu Gln Pro 
            20                  25                  30          


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


Gln Leu Gln 
    50      


<210>  37
<211>  209
<212>  PRT
<213>  Chondrus crispus

<400>  37

Met Pro Glu Ile Lys Leu Thr Tyr Phe Asp Met Arg Gly Arg Ala Glu 
1               5                   10                  15      


Ala Ser Arg Leu Ala Leu Val Val Gly Glu Ile Pro Phe Glu Asp Glu 
            20                  25                  30          


Arg Val Val Phe Asp His Trp Lys Glu Ala Lys Pro Lys Thr Pro Tyr 
        35                  40                  45              


Ala Ala Leu Pro Met Leu Thr Val Asp Gly Met Gln Val Ala Gln Ser 
    50                  55                  60                  


Asp Ala Ile Leu Arg Tyr Cys Gly Lys Leu Ala Gly Leu Tyr Pro Ser 
65                  70                  75                  80  


Asp Pro Leu Glu Ala Ala Lys Val Asp Glu Val Gly Gly Val Ile Asp 
                85                  90                  95      


Asp Val Thr His Ala Met Tyr Arg Tyr Arg Gly Asp Asp Lys Asp Lys 
            100                 105                 110         


Leu Arg Glu Glu Arg Asp Lys Phe Ser Lys Val Asp Val Pro Arg Tyr 
        115                 120                 125             


Val Gly Ala Leu Glu Lys Arg Leu Glu Ala Phe Gly Asp Gly Pro Trp 
    130                 135                 140                 


Ala Val Gly Gly Asn Met Thr Ile Ala Asp Leu His Ile Cys His Leu 
145                 150                 155                 160 


Val Thr Asn Ile Arg Cys Gly Met Leu Asp Phe Val Asp Lys Asp Leu 
                165                 170                 175     


Leu Glu Gly Tyr Val Arg Ile Val Lys Ser Tyr Ser Ala Val Met Glu 
            180                 185                 190         


His Pro Lys Val Thr Glu Trp Tyr Glu Lys Lys Pro Val Lys Met Phe 
        195                 200                 205             


Ser 
    


<210>  38
<211>  396
<212>  PRT
<213>  Escherichia coli

<400>  38

Met Lys Ile Lys Thr Gly Ala Arg Ile Leu Ala Leu Ser Ala Leu Thr 
1               5                   10                  15      


Thr Met Met Phe Ser Ala Ser Ala Leu Ala Lys Ile Glu Glu Gly Lys 
            20                  25                  30          


Leu Val Ile Trp Ile Asn Gly Asp Lys Gly Tyr Asn Gly Leu Ala Glu 
        35                  40                  45              


Val Gly Lys Lys Phe Glu Lys Asp Thr Gly Ile Lys Val Thr Val Glu 
    50                  55                  60                  


His Pro Asp Lys Leu Glu Glu Lys Phe Pro Gln Val Ala Ala Thr Gly 
65                  70                  75                  80  


Asp Gly Pro Asp Ile Ile Phe Trp Ala His Asp Arg Phe Gly Gly Tyr 
                85                  90                  95      


Ala Gln Ser Gly Leu Leu Ala Glu Ile Thr Pro Asp Lys Ala Phe Gln 
            100                 105                 110         


Asp Lys Leu Tyr Pro Phe Thr Trp Asp Ala Val Arg Tyr Asn Gly Lys 
        115                 120                 125             


Leu Ile Ala Tyr Pro Ile Ala Val Glu Ala Leu Ser Leu Ile Tyr Asn 
    130                 135                 140                 


Lys Asp Leu Leu Pro Asn Pro Pro Lys Thr Trp Glu Glu Ile Pro Ala 
145                 150                 155                 160 


Leu Asp Lys Glu Leu Lys Ala Lys Gly Lys Ser Ala Leu Met Phe Asn 
                165                 170                 175     


Leu Gln Glu Pro Tyr Phe Thr Trp Pro Leu Ile Ala Ala Asp Gly Gly 
            180                 185                 190         


Tyr Ala Phe Lys Tyr Glu Asn Gly Lys Tyr Asp Ile Lys Asp Val Gly 
        195                 200                 205             


Val Asp Asn Ala Gly Ala Lys Ala Gly Leu Thr Phe Leu Val Asp Leu 
    210                 215                 220                 


Ile Lys Asn Lys His Met Asn Ala Asp Thr Asp Tyr Ser Ile Ala Glu 
225                 230                 235                 240 


Ala Ala Phe Asn Lys Gly Glu Thr Ala Met Thr Ile Asn Gly Pro Trp 
                245                 250                 255     


Ala Trp Ser Asn Ile Asp Thr Ser Lys Val Asn Tyr Gly Val Thr Val 
            260                 265                 270         


Leu Pro Thr Phe Lys Gly Gln Pro Ser Lys Pro Phe Val Gly Val Leu 
        275                 280                 285             


Ser Ala Gly Ile Asn Ala Ala Ser Pro Asn Lys Glu Leu Ala Lys Glu 
    290                 295                 300                 


Phe Leu Glu Asn Tyr Leu Leu Thr Asp Glu Gly Leu Glu Ala Val Asn 
305                 310                 315                 320 


Lys Asp Lys Pro Leu Gly Ala Val Ala Leu Lys Ser Tyr Glu Glu Glu 
                325                 330                 335     


Leu Ala Lys Asp Pro Arg Ile Ala Ala Thr Met Glu Asn Ala Gln Lys 
            340                 345                 350         


Gly Glu Ile Met Pro Asn Ile Pro Gln Met Ser Ala Phe Trp Tyr Ala 
        355                 360                 365             


Val Arg Thr Ala Val Ile Asn Ala Ala Ser Gly Arg Gln Thr Val Asp 
    370                 375                 380                 


Glu Ala Leu Lys Asp Ala Gln Thr Arg Ile Thr Lys 
385                 390                 395     


<210>  39
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  39

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


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Trp Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
        35                  40                  45              


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    50                  55                  60                  


Glu Ser Thr Tyr Arg Trp Ser Val Leu Thr Val Leu His Gln Asp Trp 
65                  70                  75                  80  


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                85                  90                  95      


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
            100                 105         


<210>  40
<211>  106
<212>  PRT
<213>  Homo sapiens

<400>  40

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
1               5                   10                  15      


Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
            20                  25                  30          


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
        35                  40                  45              


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
    50                  55                  60                  


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
65                  70                  75                  80  


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                85                  90                  95      


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            100                 105     


<210>  41
<211>  222
<212>  PRT
<213>  Homo sapiens

<400>  41

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  42
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with the mutations 
       L234A, L235A

<400>  42

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  43
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a T366S, 368A, 
       and Y407V mutation

<400>  43

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  44
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a knob mutation

<400>  44

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  45
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a L234A, L235A 
       and hole mutation

<400>  45

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  46
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a L234A, L235A 
       and knob mutation

<400>  46

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  47
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a P329G mutation

<400>  47

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  48
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a L234A, L235A 
       and P329G mutation

<400>  48

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  49
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a P239G and hole
       mutation

<400>  49

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  50
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a P329G and knob
       mutation

<400>  50

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  51
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a L234A, L235A, 
       P329G and hole mutation

<400>  51

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  52
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG1 isotype with a L234A, L235A, 
       P329G and knob mutation

<400>  52

Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
65                  70                  75                  80  


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
    130                 135                 140                 


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


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


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220         


<210>  53
<211>  222
<212>  PRT
<213>  Homo sapiens

<400>  53

Cys Pro Ser Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


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


Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


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


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


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


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


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


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


Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    210                 215                 220         


<210>  54
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG4 isotype with a S228P and 
       L235E mutation

<400>  54

Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


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


Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


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


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


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


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


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


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


Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    210                 215                 220         


<210>  55
<211>  222
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  variant human Fc-region of the IgG4 isotype with a S228P, L235E 
       and P329G mutation

<400>  55

Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


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


Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


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


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Gly Leu Gly Ser Ser Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


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


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


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


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


Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    210                 215                 220         


<210>  56
<211>  10
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  X = S or P

<400>  56

Asp Lys Thr His Thr Cys Pro Xaa Cys Pro 
1               5                   10  


<210>  57
<211>  7
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X = S or P

<400>  57

His Thr Cys Pro Xaa Cys Pro 
1               5           


<210>  58
<211>  5
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X = S or P

<400>  58

Cys Pro Xaa Cys Pro 
1               5   


<210>  59
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pertuzumab heavy chain variable domain combined with a human 
       heavy chain constant region of the subclass IgG1 containing a 
       T366W mutation

<400>  59

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asp Tyr 
            20                  25                  30          


Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr Asn Gln Arg Phe 
    50                  55                  60                  


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


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


Ala Arg Asn Leu Gly Pro Ser Phe Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         


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


Lys 
    


<210>  60
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pertuzumab light chain variable domain combined with a human 
       kappa light chain constant region

<400>  60

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 Lys Ala Ser Gln Asp Val Ser Ile Gly 
            20                  25                  30          


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


Tyr Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gln Gly Thr Lys Val 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>  61
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Trastuzumab heavy chain variable domain combined with a human 
       heavy chain constant region of the subclass IgG1 containing a 
       T366S, L368A, and Y407V mutation

<400>  61

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
            20                  25                  30          


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


Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  62
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Trastuzumab light chain variable domain combined with a human 
       kappa light chain constant region

<400>  62

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


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


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


Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gln Gly Thr Lys Val 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>  63
<211>  241
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Pertuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal GGGSLPETGGSGSHHHHHH 
       amino acid sequence

<400>  63

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asp Tyr 
            20                  25                  30          


Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr Asn Gln Arg Phe 
    50                  55                  60                  


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


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


Ala Arg Asn Leu Gly Pro Ser Phe Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Gly Ser Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His His 
225                 230                 235                 240 


His 
    


<210>  64
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Pertuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal GSLPETGGSGSHHHHHH 
       sequence

<400>  64

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asp Tyr 
            20                  25                  30          


Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr Asn Gln Arg Phe 
    50                  55                  60                  


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


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


Ala Arg Asn Leu Gly Pro Ser Phe Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His His His 
225                 230                 235                 


<210>  65
<211>  237
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Pertuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal LPETGGSGSHHHHHH 
       sequence

<400>  65

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Asp Tyr 
            20                  25                  30          


Thr Met Asp Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Asp Val Asn Pro Asn Ser Gly Gly Ser Ile Tyr Asn Gln Arg Phe 
    50                  55                  60                  


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


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


Ala Arg Asn Leu Gly Pro Ser Phe Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


Glu Thr Gly Gly Ser Gly Ser His His His His His His 
225                 230                 235         


<210>  66
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Trastuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal GGGSLPETGGSGSHHHHHH 
       sequence

<400>  66

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
            20                  25                  30          


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


Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


Gly Gly Ser Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His 
225                 230                 235                 240 


His His 
        


<210>  67
<211>  240
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Trastuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal GSLPETGGSGSHHHHHH 
       sequence

<400>  67

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
            20                  25                  30          


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


Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


Ser Leu Pro Glu Thr Gly Gly Ser Gly Ser His His His His His His 
225                 230                 235                 240 


<210>  68
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody Fab fragment comprising a Trastuzumab heavy chain 
       variable domain and a human heavy chain constant region 1 (CH1) 
       of the subclass IgG1 containing a C-terminal LPETGGSGSHHHHHH 
       sequence

<400>  68

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
            20                  25                  30          


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


Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


Pro Glu Thr Gly Gly Ser Gly Ser His His His His His His 
225                 230                 235             


<210>  69
<211>  230
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366S, 368A, and Y407V mutation containing a N-terminal 
       gggdkthtcppc sequence

<400>  69

Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
1               5                   10                  15      


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


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


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


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


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


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


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


Pro Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
    130                 135                 140                 


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


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


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys 
            180                 185                 190         


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


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


Ser Leu Ser Pro Gly Lys 
225                 230 


<210>  70
<211>  226
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366S, 368A, and Y407V mutation containing a N-terminal gghtcppc 
       sequence

<400>  70

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


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
            20                  25                  30          


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
        35                  40                  45              


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
    50                  55                  60                  


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
65                  70                  75                  80  


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
                85                  90                  95      


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


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


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
    130                 135                 140                 


Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
145                 150                 155                 160 


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


Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 
            180                 185                 190         


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
        195                 200                 205             


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


Gly Lys 
225     


<210>  71
<211>  224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366S, 368A, and Y407V mutation containing a N-terminal ggcppc 
       sequence

<400>  71

Gly Gly Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
1               5                   10                  15      


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
            20                  25                  30          


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
        35                  40                  45              


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
    50                  55                  60                  


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
65                  70                  75                  80  


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
                85                  90                  95      


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
            100                 105                 110         


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


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 
    130                 135                 140                 


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
145                 150                 155                 160 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
                165                 170                 175     


Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 
            180                 185                 190         


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
        195                 200                 205             


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220                 


<210>  72
<211>  230
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366W mutation containing a N-terminal gggdkthtcppc sequence

<400>  72

Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
1               5                   10                  15      


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


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


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


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


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


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


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


Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn 
    130                 135                 140                 


Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
145                 150                 155                 160 


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


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


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


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


Ser Leu Ser Pro Gly Lys 
225                 230 


<210>  73
<211>  226
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366W mutations containing a N-terminal gghtcppc sequence

<400>  73

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


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
            20                  25                  30          


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
        35                  40                  45              


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
    50                  55                  60                  


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
65                  70                  75                  80  


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
                85                  90                  95      


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


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


Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
    130                 135                 140                 


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


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
        195                 200                 205             


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


Gly Lys 
225     


<210>  74
<211>  224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain Fc-region polypeptide (human IgG1(CH2-CH3)) with 
       T366W mutation containing a N-terminal ggcppc sequence

<400>  74

Gly Gly Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
1               5                   10                  15      


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
            20                  25                  30          


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
        35                  40                  45              


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
    50                  55                  60                  


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
65                  70                  75                  80  


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
                85                  90                  95      


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
            100                 105                 110         


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


Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 
    130                 135                 140                 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
145                 150                 155                 160 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
                165                 170                 175     


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


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
        195                 200                 205             


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220                 


