                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Novel antibody format

<130>   P32965-WO

<150>  EP16177746.1
<151>  2016-07-04

<160>  25    

<170>  PatentIn version 3.5

<210>  1
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-1

<400>  1

Thr Val Ser Ser Gly Gly Gly Pro Arg Glu Pro 
1               5                   10      


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

<220>
<223>  linker-2

<400>  2

Leu Ser Leu Ser Gly Gly Gly 
1               5           


<210>  3
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-3

<400>  3

Thr Val Ser Ser Gly Gly Gly Gly Ser Pro Arg Glu Pro 
1               5                   10              


<210>  4
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-4

<400>  4

Leu Ser Leu Ser Gly Gly Gly Gly Ser 
1               5                   


<210>  5
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-5

<400>  5

Thr Val Ser Ser Gly Pro Gly Pro Arg Glu Pro 
1               5                   10      


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

<220>
<223>  linker-6

<400>  6

Leu Ser Leu Ser Gly Pro Gly 
1               5           


<210>  7
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-7

<400>  7

Thr Val Ser Ser Gly Pro Pro Ser Arg Glu Pro 
1               5                   10      


<210>  8
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker-8

<400>  8

Leu Ser Leu Ser Pro Pro Gly 
1               5           


<210>  9
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal cap-1

<400>  9

Gly Ser Glu Pro Glu Ala 
1               5       


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

<220>
<223>  CH3-hole

<400>  10

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


Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 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 Val 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 Lys 
            100                 105         


<210>  11
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH3-knob

<400>  11

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


Glu Leu Thr Lys Asn Gln Val Ser Leu Trp 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 Lys 
            100                 105         


<210>  12
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH3-hole-C

<400>  12

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


Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 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 Val 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 Cys Asn His Tyr 
                85                  90                  95      


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


<210>  13
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH3-knob-C

<400>  13

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


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


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


<210>  14
<211>  123
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain VH,  <VEGF>ranibizumab

<400>  14

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 Tyr Asp Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  


Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser 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      


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


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


<210>  15
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH,  <VEGF>ranibizumab, C-variant

<400>  15

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 Tyr Asp Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  


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


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


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


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


<210>  16
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain VL,  <VEGF>ranibizumab

<400>  16

Asp 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 Ser Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          


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


Tyr Phe Thr Ser Ser Leu His 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 Tyr Ser Thr Val Pro Trp 
                85                  90                  95      


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


<210>  17
<211>  129
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain VH, <ANG-2> Ang2

<400>  17

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 Gly Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val Thr Met Thr Arg 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 Ser Pro Asn Pro Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr 
            100                 105                 110         


Pro Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser 
        115                 120                 125             


Ser 
    


<210>  18
<211>  129
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain VH, <ANG-2> Ang2, C-variant

<400>  18

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 Gly Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Ser Pro Asn Pro Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr 
            100                 105                 110         


Pro Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser 
        115                 120                 125             


Ser 
    


<210>  19
<211>  108
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain VL, <ANG-2> Ang2

<400>  19

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


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


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


Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  


Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ser Ser Asp His 
                85                  90                  95      


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


<210>  20
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal cap-2

<400>  20

Ala Ser Glu Pro Glu Ala 
1               5       


<210>  21
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  21

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


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


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


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


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  22
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  22

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


Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe 
            20                  25                  30          


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


Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys 
    50                  55                  60                  


Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser 
65                  70                  75                  80  


His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu 
                85                  90                  95      


Lys Thr Val Ala Pro Thr Glu Cys Ser 
            100                 105 


<210>  23
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  23

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>  24
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  24

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 
            100                 105 


<210>  25
<211>  98
<212>  PRT
<213>  Homo sapiens

<400>  25

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


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


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


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


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


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


Lys Val 
        


