                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>   Antibodies binding to human and cynomolgus CD3 epsilon

<130>  P32142-WO

<150>  EP14170140
<151>  2014-05-28

<150>  EP14180572
<151>  2014-08-11

<160>  34    

<170>  PatentIn version 3.5

<210>  1
<211>  20
<212>  PRT
<213>  Homo sapiens

<400>  1

Tyr Pro Arg Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu Tyr Leu 
1               5                   10                  15      


Arg Ala Arg Val 
            20  


<210>  2
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  2

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


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


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


Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp His Leu Ser Leu Lys 
    50                  55                  60                  


Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg 
65                  70                  75                  80  


Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu Tyr Leu Arg Ala Arg 
                85                  90                  95      


Val Cys Glu Asn Cys Met Glu Met Asp 
            100                 105 


<210>  3
<211>  207
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Gln Ser Gly Thr His Trp Arg Val Leu Gly Leu Cys Leu Leu Ser 
1               5                   10                  15      


Val Gly Val Trp Gly Gln Asp Gly Asn Glu Glu Met Gly Gly Ile Thr 
            20                  25                  30          


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


Cys Pro Gln Tyr Pro Gly Ser Glu Ile Leu Trp Gln His Asn Asp Lys 
    50                  55                  60                  


Asn Ile Gly Gly Asp Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp 
65                  70                  75                  80  


His Leu Ser Leu Lys Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr 
                85                  90                  95      


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


Tyr Leu Arg Ala Arg Val Cys Glu Asn Cys Met Glu Met Asp Val Met 
        115                 120                 125             


Ser Val Ala Thr Ile Val Ile Val Asp Ile Cys Ile Thr Gly Gly Leu 
    130                 135                 140                 


Leu Leu Leu Val Tyr Tyr Trp Ser Lys Asn Arg Lys Ala Lys Ala Lys 
145                 150                 155                 160 


Pro Val Thr Arg Gly Ala Gly Ala Gly Gly Arg Gln Arg Gly Gln Asn 
                165                 170                 175     


Lys Glu Arg Pro Pro Pro Val Pro Asn Pro Asp Tyr Glu Pro Ile Arg 
            180                 185                 190         


Lys Gly Gln Arg Asp Leu Tyr Ser Gly Leu Asn Gln Arg Arg Ile 
        195                 200                 205         


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

<220>
<223>  645 HVR-H1-1

<400>  4

Ser Phe Ser Gly Thr Tyr Trp Ile Cys 
1               5                   


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

<220>
<223>  645 HVR-H1-2

<400>  5

Gly Thr Tyr Trp Ile 
1               5   


<210>  6
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  645HVR-H2-1

<400>  6

Cys Ile Ser Thr Asp Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala 
1               5                   10                  15  


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

<220>
<223>  645HVR-H2-2

<400>  7

Thr Asp Ser Gly Ser Thr Tyr Tyr Ala Ser Trp 
1               5                   10      


<210>  8
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  645HVR-H2-3

<400>  8

Thr Asp Ser 
1           


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

<220>
<223>  645HVR-H3

<400>  9

Ser Ala Tyr Ala Ser Glu Gly Tyr Ala Leu 
1               5                   10  


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

<220>
<223>  645HVR-L1-1

<400>  10

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


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

<220>
<223>  645HVR-L1-2

<400>  11

Gln Ala Ser Glu Ser Val Tyr Asn Asn Asn 
1               5                   10  


<210>  12
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  645HVR-L2

<400>  12

Tyr Ala Ser Thr Leu Ala 
1               5       


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

<220>
<223>  645HVR-L3

<400>  13

Thr Gly Trp Lys Ser Ile Thr Thr Asp Gly Met Gly Ala 
1               5                   10              


<210>  14
<211>  159
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  645 VH

<400>  14

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


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


Gly Ala Ser Leu Thr Leu Thr Cys Leu Ala Ser Gly Phe Ser Phe Ser 
        35                  40                  45              


Gly Thr Tyr Trp Ile Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Cys Ile Ser Thr Asp Ser Gly Ser Thr Tyr Tyr Ala 
65                  70                  75                  80  


Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Lys Thr Ser Ser Thr Thr 
                85                  90                  95      


Val Thr Leu Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Asn 
            100                 105                 110         


Phe Cys Ala Arg Ser Ala Tyr Ala Ser Glu Gly Tyr Ala Leu Trp Gly 
        115                 120                 125             


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


Val Phe Pro Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr 
145                 150                 155                 


<210>  15
<211>  166
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  645 VL


<220>
<221>  misc_feature
<222>  (3)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  15

Met Asp Xaa Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Pro Gly Ala Thr Phe Ala Ile Val Met Thr Gln Thr Pro Ser Ser 
            20                  25                  30          


Lys Ser Val Pro Val Gly Asp Thr Val Thr Ile Asn Cys Gln Ala Ser 
        35                  40                  45              


Glu Ser Val Tyr Asn Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Pro 
    50                  55                  60                  


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


Gly Val Ser Ser Arg Phe Lys Gly Ser Gly Ser Gly Thr Gln Phe Thr 
                85                  90                  95      


Leu Thr Ile Ser Asp Val Val Cys Asp Asp Ala Ala Thr Tyr Tyr Cys 
            100                 105                 110         


Thr Gly Trp Lys Ser Ile Thr Thr Asp Gly Met Gly Ala Phe Gly Gly 
        115                 120                 125             


Gly Thr Glu Val Val Val Lys Gly Asp Pro Val Ala Pro Thr Val Leu 
    130                 135                 140                 


Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly Thr Val Thr Ile 
145                 150                 155                 160 


Val Cys Val Ala Asn Lys 
                165     


<210>  16
<211>  461
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3g(G4S)5CD3e-AcTev-Fc(knob)-Avi

<400>  16

Gln Ser Ile Lys Gly Asn His Leu Val Lys Val Tyr Asp Tyr Gln Glu 
1               5                   10                  15      


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


Trp Phe Lys Asp Gly Lys Met Ile Gly Phe Leu Thr Glu Asp Lys Lys 
        35                  40                  45              


Lys Trp Asn Leu Gly Ser Asn Ala Lys Asp Pro Arg Gly Met Tyr Gln 
    50                  55                  60                  


Cys Lys Gly Ser Gln Asn Lys Ser Lys Pro Leu Gln Val Tyr Tyr Arg 
65                  70                  75                  80  


Met Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
                85                  90                  95      


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Gly Asn Glu Glu Met 
            100                 105                 110         


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


Val Ile Leu Thr Cys Pro Gln Tyr Pro Gly Ser Glu Ile Leu Trp Gln 
    130                 135                 140                 


His Asn Asp Lys Asn Ile Gly Gly Asp Glu Asp Asp Lys Asn Ile Gly 
145                 150                 155                 160 


Ser Asp Glu Asp His Leu Ser Leu Lys Glu Phe Ser Glu Leu Glu Gln 
                165                 170                 175     


Ser Gly Tyr Tyr Val Cys Tyr Pro Arg Gly Ser Lys Pro Glu Asp Ala 
            180                 185                 190         


Asn Phe Tyr Leu Tyr Leu Arg Ala Arg Val Gly Ser Glu Gln Leu Tyr 
        195                 200                 205             


Phe Gln Gly Gly Ser Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro 
    210                 215                 220                 


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


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


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
            260                 265                 270         


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


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


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


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


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


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


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


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


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


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


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly Leu 
        435                 440                 445             


Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu 
    450                 455                 460     


<210>  17
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc(hole)

<400>  17

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
225         


<210>  18
<211>  452
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cynomolgus CD3g(G4S)5CD3e-AcTev-Fc(knob)-Avi

<400>  18

Gln Ser Phe Glu Glu Asn Arg Lys Leu Asn Val Tyr Asn Gln Glu Asp 
1               5                   10                  15      


Gly Ser Val Leu Leu Thr Cys His Val Lys Asn Thr Asn Ile Thr Trp 
            20                  25                  30          


Phe Lys Glu Gly Lys Met Ile Asp Ile Leu Thr Ala His Lys Asn Lys 
        35                  40                  45              


Trp Asn Leu Gly Ser Asn Thr Lys Asp Pro Arg Gly Val Tyr Gln Cys 
    50                  55                  60                  


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


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                85                  90                  95      


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Asp Gly Asn Glu Glu Met 
            100                 105                 110         


Gly Ser Ile Thr Gln Thr Pro Tyr Gln Val Ser Ile Ser Gly Thr Thr 
        115                 120                 125             


Val Ile Leu Thr Cys Ser Gln His Leu Gly Ser Glu Ala Gln Trp Gln 
    130                 135                 140                 


His Asn Gly Lys Asn Lys Glu Asp Ser Gly Asp Arg Leu Phe Leu Pro 
145                 150                 155                 160 


Glu Phe Ser Glu Met Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg 
                165                 170                 175     


Gly Ser Asn Pro Glu Asp Ala Ser His His Leu Tyr Leu Lys Ala Arg 
            180                 185                 190         


Val Gly Ser Glu Gln Leu Tyr Phe Gln Gly Gly Ser Pro Lys Ser Ala 
        195                 200                 205             


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
    210                 215                 220                 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
225                 230                 235                 240 


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                245                 250                 255     


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            260                 265                 270         


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
        275                 280                 285             


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


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
305                 310                 315                 320 


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                325                 330                 335     


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
            340                 345                 350         


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        355                 360                 365             


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    370                 375                 380                 


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


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                405                 410                 415     


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            420                 425                 430         


Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile 
        435                 440                 445             


Glu Trp His Glu 
    450         


<210>  19
<211>  360
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3e-stalk-Fc(knob)-Avi

<400>  19

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


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


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


Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu Asp His Leu Ser Leu Lys 
    50                  55                  60                  


Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg 
65                  70                  75                  80  


Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr Leu Tyr Leu Arg Ala Arg 
                85                  90                  95      


Val Ser Glu Asn Cys Val Asp Glu Gln Leu Tyr Phe Gln Gly Gly Ser 
            100                 105                 110         


Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
        115                 120                 125             


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
    130                 135                 140                 


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
145                 150                 155                 160 


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                165                 170                 175     


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
            180                 185                 190         


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
        195                 200                 205             


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
    210                 215                 220                 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
225                 230                 235                 240 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys 
                245                 250                 255     


Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
            260                 265                 270         


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
        275                 280                 285             


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
    290                 295                 300                 


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


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                325                 330                 335     


Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe Glu 
            340                 345                 350         


Ala Gln Lys Ile Glu Trp His Glu 
        355                 360 


<210>  20
<211>  325
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3d-stalk-Fc(hole)-Avi

<400>  20

Phe Lys Ile Pro Ile Glu Glu Leu Glu Asp Arg Val Phe Val Asn Cys 
1               5                   10                  15      


Asn Thr Ser Ile Thr Trp Val Glu Gly Thr Val Gly Thr Leu Leu Ser 
            20                  25                  30          


Asp Ile Thr Arg Leu Asp Leu Gly Lys Arg Ile Leu Asp Pro Arg Gly 
        35                  40                  45              


Ile Tyr Arg Cys Asn Gly Thr Asp Ile Tyr Lys Asp Lys Glu Ser Thr 
    50                  55                  60                  


Val Gln Val His Tyr Arg Met Cys Arg Ser Glu Gln Leu Tyr Phe Gln 
65                  70                  75                  80  


Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                85                  90                  95      


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            100                 105                 110         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        115                 120                 125             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    130                 135                 140                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
145                 150                 155                 160 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                165                 170                 175     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            180                 185                 190         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        195                 200                 205             


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


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
225                 230                 235                 240 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                245                 250                 255     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
            260                 265                 270         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        275                 280                 285             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    290                 295                 300                 


Ser Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys 
305                 310                 315                 320 


Ile Glu Trp His Glu 
                325 


<210>  21
<211>  337
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3gC85-stalk-Fc(hole)-Avi

<400>  21

Gln Ser Ile Lys Gly Asn His Leu Val Lys Val Tyr Asp Tyr Gln Glu 
1               5                   10                  15      


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


Trp Phe Lys Asp Gly Lys Met Ile Gly Phe Leu Thr Glu Asp Lys Lys 
        35                  40                  45              


Lys Trp Asn Leu Gly Ser Asn Ala Lys Asp Pro Arg Gly Met Tyr Gln 
    50                  55                  60                  


Cys Lys Gly Ser Gln Asn Lys Ser Lys Pro Leu Gln Val Tyr Tyr Arg 
65                  70                  75                  80  


Met Cys Gln Asn Gly Ser Glu Gln Leu Tyr Phe Gln Gly Asp Lys Thr 
                85                  90                  95      


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
            100                 105                 110         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
        115                 120                 125             


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    130                 135                 140                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
145                 150                 155                 160 


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


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            180                 185                 190         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        195                 200                 205             


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


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 
225                 230                 235                 240 


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                245                 250                 255     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            260                 265                 270         


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


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    290                 295                 300                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
305                 310                 315                 320 


Ser Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His 
                325                 330                 335     


Glu 
    


<210>  22
<211>  351
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cynomolgus CD3e stalk-Fc(knob)-Avi

<400>  22

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


Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr Cys Ser Gln His Leu 
            20                  25                  30          


Gly Ser Glu Ala Gln Trp Gln His Asn Gly Lys Asn Lys Glu Asp Ser 
        35                  40                  45              


Gly Asp Arg Leu Phe Leu Pro Glu Phe Ser Glu Met Glu Gln Ser Gly 
    50                  55                  60                  


Tyr Tyr Val Cys Tyr Pro Arg Gly Ser Asn Pro Glu Asp Ala Ser His 
65                  70                  75                  80  


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


Leu Tyr Phe Gln Gly Gly Ser Pro Lys Ser Ala Asp Lys Thr His Thr 
            100                 105                 110         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        115                 120                 125             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    130                 135                 140                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
145                 150                 155                 160 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                165                 170                 175     


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
            180                 185                 190         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        195                 200                 205             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    210                 215                 220                 


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


Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 
                245                 250                 255     


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


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        275                 280                 285             


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
305                 310                 315                 320 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly 
                325                 330                 335     


Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu 
            340                 345                 350     


<210>  23
<211>  334
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cynomolgus CD3d-stalk-Fc(hole)-Avi

<400>  23

Phe Lys Ile Pro Val Glu Glu Leu Glu Asp Arg Val Phe Val Lys Cys 
1               5                   10                  15      


Asn Thr Ser Val Thr Trp Val Glu Gly Thr Val Gly Thr Leu Leu Thr 
            20                  25                  30          


Asn Asn Thr Arg Leu Asp Leu Gly Lys Arg Ile Leu Asp Pro Arg Gly 
        35                  40                  45              


Ile Tyr Arg Cys Asn Gly Thr Asp Ile Tyr Lys Asp Lys Glu Ser Ala 
    50                  55                  60                  


Val Gln Val His Tyr Arg Met Ser Gln Asn Cys Val Asp Glu Gln Leu 
65                  70                  75                  80  


Tyr Phe Gln Gly Gly Ser Pro Lys Ser Ala Asp Lys Thr His Thr Cys 
                85                  90                  95      


Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 
            100                 105                 110         


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
        115                 120                 125             


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
    130                 135                 140                 


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
145                 150                 155                 160 


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


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
            180                 185                 190         


Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
        195                 200                 205             


Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser 
    210                 215                 220                 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys 
225                 230                 235                 240 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                245                 250                 255     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            260                 265                 270         


Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        275                 280                 285             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    290                 295                 300                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly 
305                 310                 315                 320 


Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu 
                325                 330                 


<210>  24
<211>  286
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3e 1-27 - Fc(knob)Avi

<400>  24

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


Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr Gly Ser Glu Gln Leu 
            20                  25                  30          


Tyr Phe Gln Gly Gly Ser Pro Lys Ser Ala Asp Lys Thr His Thr Cys 
        35                  40                  45              


Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 
    50                  55                  60                  


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
65                  70                  75                  80  


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
                85                  90                  95      


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
            100                 105                 110         


Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
        115                 120                 125             


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
    130                 135                 140                 


Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
145                 150                 155                 160 


Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys 
                165                 170                 175     


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys 
            180                 185                 190         


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
        195                 200                 205             


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


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
225                 230                 235                 240 


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
                245                 250                 255     


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly 
            260                 265                 270         


Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu 
        275                 280                 285     


<210>  25
<211>  281
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  cynomolgus CD3e 6-27 - Fc(knob)Avi

<400>  25

Glu Met Gly Ser Ile Thr Gln Thr Pro Tyr Gln Val Ser Ile Ser Gly 
1               5                   10                  15      


Thr Thr Val Ile Leu Thr Gly Ser Glu Gln Leu Tyr Phe Gln Gly Gly 
            20                  25                  30          


Ser Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
        35                  40                  45              


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    50                  55                  60                  


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
65                  70                  75                  80  


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                85                  90                  95      


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            100                 105                 110         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        115                 120                 125             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    130                 135                 140                 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
145                 150                 155                 160 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
                165                 170                 175     


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            180                 185                 190         


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
        195                 200                 205             


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    210                 215                 220                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
225                 230                 235                 240 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                245                 250                 255     


Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe 
            260                 265                 270         


Glu Ala Gln Lys Ile Glu Trp His Glu 
        275                 280     


<210>  26
<211>  281
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3e 6-27 - Fc(knob)Avi

<400>  26

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


Thr Thr Val Ile Leu Thr Gly Ser Glu Gln Leu Tyr Phe Gln Gly Gly 
            20                  25                  30          


Ser Pro Lys Ser Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
        35                  40                  45              


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    50                  55                  60                  


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
65                  70                  75                  80  


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                85                  90                  95      


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            100                 105                 110         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        115                 120                 125             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    130                 135                 140                 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
145                 150                 155                 160 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
                165                 170                 175     


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            180                 185                 190         


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
        195                 200                 205             


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    210                 215                 220                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
225                 230                 235                 240 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                245                 250                 255     


Ser Leu Ser Leu Ser Pro Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe 
            260                 265                 270         


Glu Ala Gln Lys Ile Glu Trp His Glu 
        275                 280     


<210>  27
<211>  197
<212>  PRT
<213>  Macaca fascicularis

<400>  27

Met Gln Ser Gly Thr Arg Trp Arg Val Leu Gly Leu Cys Leu Leu Ser 
1               5                   10                  15      


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


Gln Thr Pro Tyr Gln Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr 
        35                  40                  45              


Cys Ser Gln His Leu Gly Ser Glu Ala Gln Trp Gln His Asn Gly Lys 
    50                  55                  60                  


Asn Lys Glu Asp Ser Gly Asp Arg Leu Phe Leu Pro Glu Phe Ser Glu 
65                  70                  75                  80  


Met Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg Gly Ser Asn Pro 
                85                  90                  95      


Glu Asp Ala Ser His His Leu Tyr Leu Lys Ala Arg Val Cys Glu Asn 
            100                 105                 110         


Cys Met Glu Met Asp Val Met Ala Val Ala Thr Ile Val Ile Val Asp 
        115                 120                 125             


Ile Cys Ile Thr Leu Gly Leu Leu Leu Leu Val Tyr Tyr Trp Ser Lys 
    130                 135                 140                 


Asn Arg Lys Ala Lys Ala Lys Pro Val Thr Arg Gly Ala Gly Ala Gly 
145                 150                 155                 160 


Gly Arg Gln Arg Gly Gln Asn Lys Glu Arg Pro Pro Pro Val Pro Asn 
                165                 170                 175     


Pro Asp Tyr Glu Pro Ile Arg Lys Gly Gln Gln Asp Leu Tyr Ser Gly 
            180                 185                 190         


Leu Asn Gln Arg Arg 
        195         


<210>  28
<211>  96
<212>  PRT
<213>  Macaca fascicularis

<400>  28

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


Val Ser Ile Ser Gly Thr Thr Val Ile Leu Thr Cys Ser Gln His Leu 
            20                  25                  30          


Gly Ser Glu Ala Gln Trp Gln His Asn Gly Lys Asn Lys Glu Asp Ser 
        35                  40                  45              


Gly Asp Arg Leu Phe Leu Pro Glu Phe Ser Glu Met Glu Gln Ser Gly 
    50                  55                  60                  


Tyr Tyr Val Cys Tyr Pro Arg Gly Ser Asn Pro Glu Asp Ala Ser His 
65                  70                  75                  80  


His Leu Tyr Leu Lys Ala Arg Val Cys Glu Asn Cys Met Glu Met Asp 
                85                  90                  95      


<210>  29
<211>  20
<212>  PRT
<213>  Macaca fascicularis

<400>  29

Tyr Pro Arg Gly Ser Asn Pro Glu Asp Ala Ser His His Leu Tyr Leu 
1               5                   10                  15      


Lys Ala Arg Val 
            20  


<210>  30
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer rbHCfinal.up

<400>  30
aagcttgcca ccatggagac tgggctgcgc tggcttc                                37


<210>  31
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer rbHCfinal.do

<400>  31
ccattggtga gggtgcccga g                                                 21


<210>  32
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer rbLCfinal.up

<400>  32
aagcttgcca ccatggacay gagggccccc actc                                   34


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

<220>
<223>  Primer rbLCfinal.do

<400>  33
cagagtrctg ctgaggttgt aggtac                                            26


<210>  34
<211>  355
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human CD3e(D1-5) stalk-Fc(knob)-Avi

<400>  34

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


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


Trp Gln His Asn Asp Lys Asn Ile Gly Gly Asp Glu Asp Asp Lys Asn 
        35                  40                  45              


Ile Gly Ser Asp Glu Asp His Leu Ser Leu Lys Glu Phe Ser Glu Leu 
    50                  55                  60                  


Glu Gln Ser Gly Tyr Tyr Val Cys Tyr Pro Arg Gly Ser Lys Pro Glu 
65                  70                  75                  80  


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


Val Asp Glu Gln Leu Tyr Phe Gln Gly Gly Ser Pro Lys Ser Ala Asp 
            100                 105                 110         


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
        115                 120                 125             


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
    130                 135                 140                 


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
145                 150                 155                 160 


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                165                 170                 175     


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
            180                 185                 190         


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
        195                 200                 205             


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
    210                 215                 220                 


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
225                 230                 235                 240 


Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
                245                 250                 255     


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
            260                 265                 270         


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
        275                 280                 285             


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
    290                 295                 300                 


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
305                 310                 315                 320 


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                325                 330                 335     


Gly Lys Ser Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu 
            340                 345                 350         


Trp His Glu 
        355 


