                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>   HUMANIZED ANTI-HUMAN CD19 ANTIBODIES AND METHODS OF USE

<130>  P33094

<150>  EP15187820.4
<151>  2015-10-01

<160>  70    

<170>  PatentIn version 3.5

<210>  1
<211>  121
<212>  PRT
<213>  Mus musculus

<400>  1

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


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


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


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


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


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


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


Gln Gly Thr Thr Leu Thr Val Ser Ser 
        115                 120     


<210>  2
<211>  112
<212>  PRT
<213>  Mus musculus

<400>  2

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Glu Asn Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Leu 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  3
<211>  5
<212>  PRT
<213>  Mus musculus

<400>  3

Asp Tyr Ile Met His 
1               5   


<210>  4
<211>  17
<212>  PRT
<213>  Mus musculus

<400>  4

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


Gly 
    


<210>  5
<211>  12
<212>  PRT
<213>  Mus musculus

<400>  5

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


<210>  6
<211>  16
<212>  PRT
<213>  Mus musculus

<400>  6

Arg Ser Ser Gln Ser Leu Glu Asn Ser Asn Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  7
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  7

Arg Val Ser Lys Arg Phe Ser 
1               5           


<210>  8
<211>  9
<212>  PRT
<213>  Mus musculus

<400>  8

Leu Gln Leu Thr His Val Pro Tyr Thr 
1               5                   


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

<220>
<223>  humanized VH

<400>  9

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


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


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


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


Gln Gly Arg Val Thr Met Thr Ser Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  10
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N27dH VL

<400>  10

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu His Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  11
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized HVR-H2

<400>  11

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


Gly 
    


<210>  12
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N27dH HVR-L1

<400>  12

Lys Ser Ser Gln Ser Leu Glu His Ser Asn Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  13
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N27dQ VL

<400>  13

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Gln Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  14
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N27dQ HVR-L1

<400>  14

Lys Ser Ser Gln Ser Leu Glu Gln Ser Asn Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  15
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eA VH

<400>  15

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Ala 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


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

<220>
<223>  S27eA HVR-L1

<400>  16

Lys Ser Ser Gln Ser Leu Glu Asn Ala Asn Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  17
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eV VL

<400>  17

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Val 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  18
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eV HVR-L1

<400>  18

Lys Ser Ser Gln Ser Leu Glu Asn Val Asn Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  19
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eP VL

<400>  19

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Pro 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  20
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eP HVR-L1

<400>  20

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


<210>  21
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N28Q VL

<400>  21

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  22
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N28Q HVR-L1

<400>  22

Lys Ser Ser Gln Ser Leu Glu Asn Ser Gln Gly Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  23
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G29A VL

<400>  23

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  24
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G29A HVR-L1

<400>  24

Lys Ser Ser Gln Ser Leu Glu Asn Ser Asn Ala Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  25
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G29V VL

<400>  25

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  26
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  G29V HVR-L1

<400>  26

Lys Ser Ser Gln Ser Leu Glu Asn Ser Asn Val Asn Thr Tyr Leu Asn 
1               5                   10                  15      


<210>  27
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eP/N28S VH

<400>  27

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Glu Asn Pro 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Leu Gln Leu 
                85                  90                  95      


Thr His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  28
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S27eP/N28S HVR-L1

<400>  28

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


<210>  29
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  signal peptide

<400>  29

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


Val His Ser 
            


<210>  30
<211>  272
<212>  PRT
<213>  Homo sapiens

<400>  30

Pro Glu Glu Pro Leu Val Val Lys Val Glu Glu Gly Asp Asn Ala Val 
1               5                   10                  15      


Leu Gln Cys Leu Lys Gly Thr Ser Asp Gly Pro Thr Gln Gln Leu Thr 
            20                  25                  30          


Trp Ser Arg Glu Ser Pro Leu Lys Pro Phe Leu Lys Leu Ser Leu Gly 
        35                  40                  45              


Leu Pro Gly Leu Gly Ile His Met Arg Pro Leu Ala Ile Trp Leu Phe 
    50                  55                  60                  


Ile Phe Asn Val Ser Gln Gln Met Gly Gly Phe Tyr Leu Cys Gln Pro 
65                  70                  75                  80  


Gly Pro Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr Val Asn Val 
                85                  90                  95      


Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp Leu Gly Gly 
            100                 105                 110         


Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro Ser Ser Pro 
        115                 120                 125             


Ser Gly Lys Leu Met Ser Pro Lys Leu Tyr Val Trp Ala Lys Asp Arg 
    130                 135                 140                 


Pro Glu Ile Trp Glu Gly Glu Pro Pro Cys Leu Pro Pro Arg Asp Ser 
145                 150                 155                 160 


Leu Asn Gln Ser Leu Ser Gln Asp Leu Thr Met Ala Pro Gly Ser Thr 
                165                 170                 175     


Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser Arg Gly Pro 
            180                 185                 190         


Leu Ser Trp Thr His Val His Pro Lys Gly Pro Lys Ser Leu Leu Ser 
        195                 200                 205             


Leu Glu Leu Lys Asp Asp Arg Pro Ala Arg Asp Met Trp Val Met Glu 
    210                 215                 220                 


Thr Gly Leu Leu Leu Pro Arg Ala Thr Ala Gln Asp Ala Gly Lys Tyr 
225                 230                 235                 240 


Tyr Cys His Arg Gly Asn Leu Thr Met Ser Phe His Leu Glu Ile Thr 
                245                 250                 255     


Ala Arg Pro Val Leu Trp His Trp Leu Leu Arg Thr Gly Gly Trp Lys 
            260                 265                 270         


<210>  31
<211>  274
<212>  PRT
<213>  Macaca fascicularis

<400>  31

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


Leu Gln Cys Leu Glu Gly Thr Ser Asp Gly Pro Thr Gln Gln Leu Val 
            20                  25                  30          


Trp Cys Arg Asp Ser Pro Phe Glu Pro Phe Leu Asn Leu Ser Leu Gly 
        35                  40                  45              


Leu Pro Gly Met Gly Ile Arg Met Gly Pro Leu Gly Ile Trp Leu Leu 
    50                  55                  60                  


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


Gly Leu Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr Val Ser Val 
                85                  90                  95      


Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp Leu Gly Gly 
            100                 105                 110         


Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro Ser Ser Pro 
        115                 120                 125             


Ser Gly Lys Leu Asn Ser Ser Gln Leu Tyr Val Trp Ala Lys Asp Arg 
    130                 135                 140                 


Pro Glu Met Trp Glu Gly Glu Pro Val Cys Gly Pro Pro Arg Asp Ser 
145                 150                 155                 160 


Leu Asn Gln Ser Leu Ser Gln Asp Leu Thr Met Ala Pro Gly Ser Thr 
                165                 170                 175     


Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser Arg Gly Pro 
            180                 185                 190         


Leu Ser Trp Thr His Val Arg Pro Lys Gly Pro Lys Ser Ser Leu Leu 
        195                 200                 205             


Ser Leu Glu Leu Lys Asp Asp Arg Pro Asp Arg Asp Met Trp Val Val 
    210                 215                 220                 


Asp Thr Gly Leu Leu Leu Thr Arg Ala Thr Ala Gln Asp Ala Gly Lys 
225                 230                 235                 240 


Tyr Tyr Cys His Arg Gly Asn Trp Thr Lys Ser Phe Tyr Leu Glu Ile 
                245                 250                 255     


Thr Ala Arg Pro Ala Leu Trp His Trp Leu Leu Arg Ile Gly Gly Trp 
            260                 265                 270         


Lys Val 
        


<210>  32
<211>  36
<212>  PRT
<213>  Homo sapiens

<400>  32

Asp Thr Asp Leu Cys Asn Ala Ser Gly Ala His Ala Leu Gln Pro Ala 
1               5                   10                  15      


Ala Ala Ile Leu Ala Leu Leu Pro Ala Leu Gly Leu Leu Leu Trp Gly 
            20                  25                  30          


Pro Gly Gln Leu 
        35      


<210>  33
<211>  537
<212>  PRT
<213>  Homo sapiens

<400>  33

Pro Glu Glu Pro Leu Val Val Lys Val Glu Glu Gly Asp Asn Ala Val 
1               5                   10                  15      


Leu Gln Cys Leu Lys Gly Thr Ser Asp Gly Pro Thr Gln Gln Leu Thr 
            20                  25                  30          


Trp Ser Arg Glu Ser Pro Leu Lys Pro Phe Leu Lys Leu Ser Leu Gly 
        35                  40                  45              


Leu Pro Gly Leu Gly Ile His Met Arg Pro Leu Ala Ile Trp Leu Phe 
    50                  55                  60                  


Ile Phe Asn Val Ser Gln Gln Met Gly Gly Phe Tyr Leu Cys Gln Pro 
65                  70                  75                  80  


Gly Pro Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr Val Asn Val 
                85                  90                  95      


Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp Leu Gly Gly 
            100                 105                 110         


Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro Ser Ser Pro 
        115                 120                 125             


Ser Gly Lys Leu Met Ser Pro Lys Leu Tyr Val Trp Ala Lys Asp Arg 
    130                 135                 140                 


Pro Glu Ile Trp Glu Gly Glu Pro Pro Cys Leu Pro Pro Arg Asp Ser 
145                 150                 155                 160 


Leu Asn Gln Ser Leu Ser Gln Asp Leu Thr Met Ala Pro Gly Ser Thr 
                165                 170                 175     


Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser Arg Gly Pro 
            180                 185                 190         


Leu Ser Trp Thr His Val His Pro Lys Gly Pro Lys Ser Leu Leu Ser 
        195                 200                 205             


Leu Glu Leu Lys Asp Asp Arg Pro Ala Arg Asp Met Trp Val Met Glu 
    210                 215                 220                 


Thr Gly Leu Leu Leu Pro Arg Ala Thr Ala Gln Asp Ala Gly Lys Tyr 
225                 230                 235                 240 


Tyr Cys His Arg Gly Asn Leu Thr Met Ser Phe His Leu Glu Ile Thr 
                245                 250                 255     


Ala Arg Pro Val Leu Trp His Trp Leu Leu Arg Thr Gly Gly Trp Lys 
            260                 265                 270         


Val Ser Ala Val Thr Leu Ala Tyr Leu Ile Phe Cys Leu Cys Ser Leu 
        275                 280                 285             


Val Gly Ile Leu His Leu Gln Arg Ala Leu Val Leu Arg Arg Lys Arg 
    290                 295                 300                 


Lys Arg Met Thr Asp Pro Thr Arg Arg Phe Phe Lys Val Thr Pro Pro 
305                 310                 315                 320 


Pro Gly Ser Gly Pro Gln Asn Gln Tyr Gly Asn Val Leu Ser Leu Pro 
                325                 330                 335     


Thr Pro Thr Ser Gly Leu Gly Arg Ala Gln Arg Trp Ala Ala Gly Leu 
            340                 345                 350         


Gly Gly Thr Ala Pro Ser Tyr Gly Asn Pro Ser Ser Asp Val Gln Ala 
        355                 360                 365             


Asp Gly Ala Leu Gly Ser Arg Ser Pro Pro Gly Val Gly Pro Glu Glu 
    370                 375                 380                 


Glu Glu Gly Glu Gly Tyr Glu Glu Pro Asp Ser Glu Glu Asp Ser Glu 
385                 390                 395                 400 


Phe Tyr Glu Asn Asp Ser Asn Leu Gly Gln Asp Gln Leu Ser Gln Asp 
                405                 410                 415     


Gly Ser Gly Tyr Glu Asn Pro Glu Asp Glu Pro Leu Gly Pro Glu Asp 
            420                 425                 430         


Glu Asp Ser Phe Ser Asn Ala Glu Ser Tyr Glu Asn Glu Asp Glu Glu 
        435                 440                 445             


Leu Thr Gln Pro Val Ala Arg Thr Met Asp Phe Leu Ser Pro His Gly 
    450                 455                 460                 


Ser Ala Trp Asp Pro Ser Arg Glu Ala Thr Ser Leu Gly Ser Gln Ser 
465                 470                 475                 480 


Tyr Glu Asp Met Arg Gly Ile Leu Tyr Ala Ala Pro Gln Leu Arg Ser 
                485                 490                 495     


Ile Arg Gly Gln Pro Gly Pro Asn His Glu Glu Asp Ala Asp Ser Tyr 
            500                 505                 510         


Glu Asn Met Asp Asn Pro Asp Gly Pro Asp Pro Ala Trp Gly Gly Gly 
        515                 520                 525             


Gly Arg Met Gly Thr Trp Ser Thr Arg 
    530                 535         


<210>  34
<211>  538
<212>  PRT
<213>  Homo sapiens

<400>  34

Pro Glu Glu Pro Leu Val Val Lys Val Glu Glu Gly Asp Asn Ala Val 
1               5                   10                  15      


Leu Gln Cys Leu Lys Gly Thr Ser Asp Gly Pro Thr Gln Gln Leu Thr 
            20                  25                  30          


Trp Ser Arg Glu Ser Pro Leu Lys Pro Phe Leu Lys Leu Ser Leu Gly 
        35                  40                  45              


Leu Pro Gly Leu Gly Ile His Met Arg Pro Leu Ala Ile Trp Leu Phe 
    50                  55                  60                  


Ile Phe Asn Val Ser Gln Gln Met Gly Gly Phe Tyr Leu Cys Gln Pro 
65                  70                  75                  80  


Gly Pro Pro Ser Glu Lys Ala Trp Gln Pro Gly Trp Thr Val Asn Val 
                85                  90                  95      


Glu Gly Ser Gly Glu Leu Phe Arg Trp Asn Val Ser Asp Leu Gly Gly 
            100                 105                 110         


Leu Gly Cys Gly Leu Lys Asn Arg Ser Ser Glu Gly Pro Ser Ser Pro 
        115                 120                 125             


Ser Gly Lys Leu Met Ser Pro Lys Leu Tyr Val Trp Ala Lys Asp Arg 
    130                 135                 140                 


Pro Glu Ile Trp Glu Gly Glu Pro Pro Cys Leu Pro Pro Arg Asp Ser 
145                 150                 155                 160 


Leu Asn Gln Ser Leu Ser Gln Asp Leu Thr Met Ala Pro Gly Ser Thr 
                165                 170                 175     


Leu Trp Leu Ser Cys Gly Val Pro Pro Asp Ser Val Ser Arg Gly Pro 
            180                 185                 190         


Leu Ser Trp Thr His Val His Pro Lys Gly Pro Lys Ser Leu Leu Ser 
        195                 200                 205             


Leu Glu Leu Lys Asp Asp Arg Pro Ala Arg Asp Met Trp Val Met Glu 
    210                 215                 220                 


Thr Gly Leu Leu Leu Pro Arg Ala Thr Ala Gln Asp Ala Gly Lys Tyr 
225                 230                 235                 240 


Tyr Cys His Arg Gly Asn Leu Thr Met Ser Phe His Leu Glu Ile Thr 
                245                 250                 255     


Ala Arg Pro Val Leu Trp His Trp Leu Leu Arg Thr Gly Gly Trp Lys 
            260                 265                 270         


Val Ser Ala Val Thr Leu Ala Tyr Leu Ile Phe Cys Leu Cys Ser Leu 
        275                 280                 285             


Val Gly Ile Leu His Leu Gln Arg Ala Leu Val Leu Arg Arg Lys Arg 
    290                 295                 300                 


Lys Arg Met Thr Asp Pro Thr Arg Arg Phe Phe Lys Val Thr Pro Pro 
305                 310                 315                 320 


Pro Gly Ser Gly Pro Gln Asn Gln Tyr Gly Asn Val Leu Ser Leu Pro 
                325                 330                 335     


Thr Pro Thr Ser Gly Leu Gly Arg Ala Gln Arg Trp Ala Ala Gly Leu 
            340                 345                 350         


Gly Gly Thr Ala Pro Ser Tyr Gly Asn Pro Ser Ser Asp Val Gln Ala 
        355                 360                 365             


Asp Gly Ala Leu Gly Ser Arg Ser Pro Pro Gly Val Gly Pro Glu Glu 
    370                 375                 380                 


Glu Glu Gly Glu Gly Tyr Glu Glu Pro Asp Ser Glu Glu Asp Ser Glu 
385                 390                 395                 400 


Phe Tyr Glu Asn Asp Ser Asn Leu Gly Gln Asp Gln Leu Ser Gln Asp 
                405                 410                 415     


Gly Ser Gly Tyr Glu Asn Pro Glu Asp Glu Pro Leu Gly Pro Glu Asp 
            420                 425                 430         


Glu Asp Ser Phe Ser Asn Ala Glu Ser Tyr Glu Asn Glu Asp Glu Glu 
        435                 440                 445             


Leu Thr Gln Pro Val Ala Arg Thr Met Asp Phe Leu Ser Pro His Gly 
    450                 455                 460                 


Ser Ala Trp Asp Pro Ser Arg Glu Ala Thr Ser Leu Ala Gly Ser Gln 
465                 470                 475                 480 


Ser Tyr Glu Asp Met Arg Gly Ile Leu Tyr Ala Ala Pro Gln Leu Arg 
                485                 490                 495     


Ser Ile Arg Gly Gln Pro Gly Pro Asn His Glu Glu Asp Ala Asp Ser 
            500                 505                 510         


Tyr Glu Asn Met Asp Asn Pro Asp Gly Pro Asp Pro Ala Trp Gly Gly 
        515                 520                 525             


Gly Gly Arg Met Gly Thr Trp Ser Thr Arg 
    530                 535             


<210>  35
<211>  31
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody fragment for MS analysis


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

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  X = G or A

<400>  35

Ser Ser Gln Ser Leu Glu Asn Xaa Asn Xaa Asn Thr Tyr Leu Asn Trp 
1               5                   10                  15      


Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Arg 
            20                  25                  30      


<210>  36
<211>  6
<212>  PRT
<213>  Mus musculus

<400>  36

Asn Ser Asn Gly Asn Thr 
1               5       


<210>  37
<211>  4
<212>  PRT
<213>  Mus musculus

<400>  37

Lys Phe Asn Gly 
1               


<210>  38
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized HVR-H2 fragment with N64Q mutation

<400>  38

Thr Glu Lys Phe Gln Gly 
1               5       


<210>  39
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized HVR-L2 fragment with S27eP mutation

<400>  39

Leu Glu Asn Pro Asn Gly Asn Thr 
1               5               


<210>  40
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized HVR-L2 fragment with S27eP/N28S mutation

<400>  40

Leu Glu Asn Pro Ser Gly Asn Thr 
1               5               


<210>  41
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  41

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
1               5                   10                  15      


Gly Ser 
        


<210>  42
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  42

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


<210>  43
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  43

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


<210>  44
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  44

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


<210>  45
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptidic linker

<400>  45

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
            20                  25                  30          


<210>  46
<211>  118
<212>  PRT
<213>  Mus musculus

<400>  46

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


Ser Leu Thr Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


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


Ala Met Ile Tyr Tyr Asp Ser Ser Lys Met Asn Tyr Ala Asp Thr Val 
    50                  55                  60                  


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


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


Ala Val Pro Thr Ser His Tyr Val Val Asp Val Trp Gly Gln Gly Val 
            100                 105                 110         


Ser Val Thr Val Ser Ser 
        115             


<210>  47
<211>  107
<212>  PRT
<213>  Mus musculus

<400>  47

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


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


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


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


Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val 
65                  70                  75                  80  


Glu Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp 
                85                  90                  95      


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


<210>  48
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  L104V and L106I variant of SEQ ID NO: 57

<400>  48

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


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


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


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


Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val 
65                  70                  75                  80  


Glu Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp 
                85                  90                  95      


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


<210>  49
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-023 VH humanization variant_DASG

<400>  49

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


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


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


Tyr Ile Trp Ser Gly Gly Ser Thr Asp Tyr Ala Ser Trp Ala Lys Ser 
    50                  55                  60                  


Arg Val Thr Ile Ser Lys Thr Ser Thr Thr Val Ser Leu Lys Leu Ser 
65                  70                  75                  80  


Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg Tyr 
                85                  90                  95      


Gly Thr Ser Tyr Pro Asp Tyr Gly Asp Ala Ser Gly Phe Asp Pro Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  50
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-009 VL humanization variant_NYA

<400>  50

Ala Ile Gln Leu 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 Ser Ile Ser Ser Tyr 
            20                  25                  30          


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


Tyr Arg Ala Ser Thr Leu Ala Ser 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 Asn Tyr Ala Ser Ser Asn 
                85                  90                  95      


Val Asp Asn Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110 


<210>  51
<211>  7
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  51

Gly Phe Ser Leu Ser Ser Tyr 
1               5           


<210>  52
<211>  5
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  52

Trp Ser Gly Gly Ser 
1               5   


<210>  53
<211>  17
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  53

Arg Tyr Gly Thr Ser Tyr Pro Asp Tyr Gly Asp Ala Asn Gly Phe Asp 
1               5                   10                  15      


Pro 
    


<210>  54
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-000 HVR-H3 DASG

<400>  54

Arg Tyr Gly Thr Ser Tyr Pro Asp Tyr Gly Asp Ala Ser Gly Phe Asp 
1               5                   10                  15      


Pro 
    


<210>  55
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-000 HVR-H3 DAQG

<400>  55

Arg Tyr Gly Thr Ser Tyr Pro Asp Tyr Gly Asp Ala Gln Gly Phe Asp 
1               5                   10                  15      


Pro 
    


<210>  56
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-000 HVR-L1 RAA

<400>  56

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


<210>  57
<211>  7
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  57

Arg Ala Ser Thr Leu Ala Ser 
1               5           


<210>  58
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  299-000 HVR-L3 NYA

<400>  58

Gln Gln Asn Tyr Ala Ser Ser Asn Val Asp Asn Thr 
1               5                   10          


<210>  59
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 0

<400>  59

Gln Ser Leu Glu Asn Ser Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  60
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 1

<400>  60

Gln Ser Leu Glu His Ser Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  61
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 2

<400>  61

Gln Ser Leu Glu Gln Ser Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  62
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 3

<400>  62

Gln Ser Leu Glu Asn Ala Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  63
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 4

<400>  63

Gln Ser Leu Glu Asn Val Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  64
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 5

<400>  64

Gln Ser Leu Glu Asn Pro Asn Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  65
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 6

<400>  65

Gln Ser Leu Glu Asn Ser Gln Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  66
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 7

<400>  66

Gln Ser Leu Glu Asn Ser Asn Ala Asn Thr Tyr Leu 
1               5                   10          


<210>  67
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 8

<400>  67

Gln Ser Leu Glu Asn Ser Asn Val Asn Thr Tyr Leu 
1               5                   10          


<210>  68
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence LC variant 9

<400>  68

Gln Ser Leu Glu Asn Pro Ser Gly Asn Thr Tyr Leu 
1               5                   10          


<210>  69
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence HC variant 0

<400>  69

Thr Glu Lys Phe Asn Gly Lys Ala Thr Leu 
1               5                   10  


<210>  70
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  sequence HC variant 1

<400>  70

Thr Glu Lys Phe Gln Gly Arg Val Thr Met 
1               5                   10  


