                         SEQUENCE LISTING

<110>  Novo Nordisk A/S
 
<120>  Novel compounds for treatment of obesity

<130>  180007WO01

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain of anti TfR-Fab

<400>  1

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 Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


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


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  2
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain of anti TfR-Fab

<400>  2

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


Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly 
    130                 135                 140                 


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


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


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


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


Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 
    210                 215                 


<210>  3
<211>  433
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti TfR-Fab


<220>
<221>  DISULFID
<222>  (23)..(88)

<220>
<221>  DISULFID
<222>  (134)..(194)

<220>
<221>  DISULFID
<222>  (214)..(346)

<220>
<221>  DISULFID
<222>  (236)..(310)

<220>
<221>  DISULFID
<222>  (359)..(415)

<400>  3

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 Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


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


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly 
    210                 215                 220                 


Leu Val Gln Pro Gly Asn Ser Leu Thr Leu Ser Cys Val Ala Ser Gly 
225                 230                 235                 240 


Phe Thr Phe Ser Asn Tyr Gly Met His Trp Ile Arg Gln Ala Pro Lys 
                245                 250                 255     


Lys Gly Leu Glu Trp Ile Ala Met Ile Tyr Tyr Asp Ser Ser Lys Met 
            260                 265                 270         


Asn Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 
        275                 280                 285             


Ser Lys Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu Arg Ser Glu Asp 
    290                 295                 300                 


Thr Ala Met Tyr Tyr Cys Ala Val Pro Thr Ser His Tyr Val Val Asp 
305                 310                 315                 320 


Val Trp Gly Gln Gly Val Ser Val Thr Val Ser Ser Ala Ser Thr Lys 
                325                 330                 335     


Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu 
            340                 345                 350         


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


Val Thr Val Ser Trp Asn Ser Gly Cys Leu Thr Ser Gly Val His Thr 
    370                 375                 380                 


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
385                 390                 395                 400 


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn 
                405                 410                 415     


Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser 
            420                 425                 430         


Lys 
    


<210>  4
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain of control Fab

<400>  4

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 Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn 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 Ser Gln Ser 
                85                  90                  95      


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


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  5
<211>  438
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Control Fab


<220>
<221>  DISULFID
<222>  (23)..(93)

<220>
<221>  DISULFID
<222>  (139)..(199)

<220>
<221>  DISULFID
<222>  (219)..(351)

<220>
<221>  DISULFID
<222>  (241)..(315)

<220>
<221>  DISULFID
<222>  (364)..(420)

<400>  5

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 Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn 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 Ser Gln Ser 
                85                  90                  95      


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


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


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


Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Thr Leu Ser 
225                 230                 235                 240 


Cys Val Ala Ser Gly Phe Thr Phe Ser Asn Tyr Gly Met His Trp Ile 
                245                 250                 255     


Arg Gln Ala Pro Lys Lys Gly Leu Glu Trp Ile Ala Met Ile Tyr Tyr 
            260                 265                 270         


Asp Ser Ser Lys Met Asn Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr 
        275                 280                 285             


Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Glu Met Asn Ser 
    290                 295                 300                 


Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Val Pro Thr Ser 
305                 310                 315                 320 


His Tyr Val Val Asp Val Trp Gly Gln Gly Val Ser Val Thr Val Ser 
                325                 330                 335     


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
            340                 345                 350         


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
        355                 360                 365             


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Cys Leu Thr 
    370                 375                 380                 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
385                 390                 395                 400 


Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys 
                405                 410                 415     


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
            420                 425                 430         


Lys Arg Val Glu Ser Lys 
        435             


<210>  6
<211>  266
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain of GLP-1 anti TNP-Fab fusion protein

<400>  6

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Pro Gly 
            20                  25                  30          


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asp 
        35                  40                  45              


Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln 
    50                  55                  60                  


Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn 
65                  70                  75                  80  


Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro 
                85                  90                  95      


Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp 
            100                 105                 110         


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser 
        115                 120                 125             


Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser Thr 
    130                 135                 140                 


His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
145                 150                 155                 160 


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                165                 170                 175     


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
            180                 185                 190         


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
        195                 200                 205             


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
    210                 215                 220                 


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
225                 230                 235                 240 


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                245                 250                 255     


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            260                 265     


<210>  7
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain of GLP-1 anti TNP-Fab fusion protein


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  Q is pyroglutamic acid

<400>  7

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


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


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


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


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


Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Arg Tyr Gly Ser Tyr Val Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


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


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


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


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys His His His His His His His 
    210                 215                 220                 


His His His 
225         


<210>  8
<211>  493
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-1 anti TNP-Fab fusion protein


<220>
<221>  DISULFID
<222>  (70)..(140)

<220>
<221>  DISULFID
<222>  (186)..(246)

<220>
<221>  DISULFID
<222>  (266)..(396)

<220>
<221>  DISULFID
<222>  (288)..(361)

<220>
<221>  DISULFID
<222>  (409)..(465)

<400>  8

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Pro Gly 
            20                  25                  30          


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asp 
        35                  40                  45              


Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln 
    50                  55                  60                  


Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn 
65                  70                  75                  80  


Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro 
                85                  90                  95      


Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp 
            100                 105                 110         


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser 
        115                 120                 125             


Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser Thr 
    130                 135                 140                 


His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
145                 150                 155                 160 


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                165                 170                 175     


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
            180                 185                 190         


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
        195                 200                 205             


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
    210                 215                 220                 


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
225                 230                 235                 240 


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                245                 250                 255     


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gln Val Gln Leu Gln Glu 
            260                 265                 270         


Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys 
        275                 280                 285             


Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Tyr Trp Asn Trp Ile Arg 
    290                 295                 300                 


Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Thr Ile Ser Tyr Ser 
305                 310                 315                 320 


Gly Asp Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser 
                325                 330                 335     


Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr 
            340                 345                 350         


Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Tyr Gly Ser Tyr Val 
        355                 360                 365             


Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser 
    370                 375                 380                 


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr 
385                 390                 395                 400 


Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
                405                 410                 415     


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
            420                 425                 430         


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
        435                 440                 445             


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr 
    450                 455                 460                 


Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 
465                 470                 475                 480 


Glu Ser Lys His His His His His His His His His His 
                485                 490             


<210>  9
<211>  261
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain of GLP-1 anti TfR-Fab fusion protein

<400>  9

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Pro Gly 
            20                  25                  30          


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asp 
        35                  40                  45              


Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Leu Glu Glu 
    50                  55                  60                  


Ile Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Gly Asn Trp Leu 
65                  70                  75                  80  


Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile Tyr 
                85                  90                  95      


Gly Ala Thr Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly Ser 
            100                 105                 110         


Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val Glu 
        115                 120                 125             


Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp Thr 
    130                 135                 140                 


Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro 
145                 150                 155                 160 


Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly 
                165                 170                 175     


Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn 
            180                 185                 190         


Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn 
        195                 200                 205             


Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser 
    210                 215                 220                 


Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr 
225                 230                 235                 240 


Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe 
                245                 250                 255     


Asn Arg Asn Glu Cys 
            260     


<210>  10
<211>  231
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain of GLP-1 anti TfR-Fab fusion protein

<400>  10

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 Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro 
        115                 120                 125             


Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly 
    130                 135                 140                 


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


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


Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser Thr 
            180                 185                 190         


Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser 
        195                 200                 205             


Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly His His His 
    210                 215                 220                 


His His His His His His His 
225                 230     


<210>  11
<211>  492
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-1 anti TfR-fab fusion protein


<220>
<221>  DISULFID
<222>  (70)..(135)

<220>
<221>  DISULFID
<222>  (181)..(241)

<220>
<221>  DISULFID
<222>  (261)..(481)

<220>
<221>  DISULFID
<222>  (283)..(357)

<220>
<221>  DISULFID
<222>  (407)..(461)

<400>  11

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Pro Gly 
            20                  25                  30          


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asp 
        35                  40                  45              


Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Leu Glu Glu 
    50                  55                  60                  


Ile Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Gly Asn Trp Leu 
65                  70                  75                  80  


Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile Tyr 
                85                  90                  95      


Gly Ala Thr Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly Ser 
            100                 105                 110         


Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val Glu 
        115                 120                 125             


Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp Thr 
    130                 135                 140                 


Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala Pro 
145                 150                 155                 160 


Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly 
                165                 170                 175     


Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn 
            180                 185                 190         


Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn 
        195                 200                 205             


Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser 
    210                 215                 220                 


Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr 
225                 230                 235                 240 


Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe 
                245                 250                 255     


Asn Arg Asn Glu Cys Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
            260                 265                 270         


Val Gln Pro Gly Asn Ser Leu Thr Leu Ser Cys Val Ala Ser Gly Phe 
        275                 280                 285             


Thr Phe Ser Asn Tyr Gly Met His Trp Ile Arg Gln Ala Pro Lys Lys 
    290                 295                 300                 


Gly Leu Glu Trp Ile Ala Met Ile Tyr Tyr Asp Ser Ser Lys Met Asn 
305                 310                 315                 320 


Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
                325                 330                 335     


Lys Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu Arg Ser Glu Asp Thr 
            340                 345                 350         


Ala Met Tyr Tyr Cys Ala Val Pro Thr Ser His Tyr Val Val Asp Val 
        355                 360                 365             


Trp Gly Gln Gly Val Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro 
    370                 375                 380                 


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


Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val 
                405                 410                 415     


Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe 
            420                 425                 430         


Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr 
        435                 440                 445             


Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala 
    450                 455                 460                 


His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp 
465                 470                 475                 480 


Cys Gly His His His His His His His His His His 
                485                 490         


<210>  12
<211>  497
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-1 control Fab fusion protein


<220>
<221>  DISULFID
<222>  (70)..(140)

<220>
<221>  DISULFID
<222>  (186)..(246)

<220>
<221>  DISULFID
<222>  (266)..(486)

<220>
<221>  DISULFID
<222>  (288)..(362)

<220>
<221>  DISULFID
<222>  (411)..(466)

<400>  12

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Pro Gly 
            20                  25                  30          


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Asp 
        35                  40                  45              


Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln 
    50                  55                  60                  


Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn 
65                  70                  75                  80  


Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro 
                85                  90                  95      


Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro Asp 
            100                 105                 110         


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser 
        115                 120                 125             


Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser Thr 
    130                 135                 140                 


His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
145                 150                 155                 160 


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
                165                 170                 175     


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
            180                 185                 190         


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
        195                 200                 205             


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
    210                 215                 220                 


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
225                 230                 235                 240 


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
                245                 250                 255     


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Glu Val Gln Leu Val Glu 
            260                 265                 270         


Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Thr Leu Ser Cys 
        275                 280                 285             


Val Ala Ser Gly Phe Thr Phe Ser Asn Tyr Gly Met His Trp Ile Arg 
    290                 295                 300                 


Gln Ala Pro Lys Lys Gly Leu Glu Trp Ile Ala Met Ile Tyr Tyr Asp 
305                 310                 315                 320 


Ser Ser Lys Met Asn Tyr Ala Asp Thr Val Lys Gly Arg Phe Thr Ile 
                325                 330                 335     


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Glu Met Asn Ser Leu 
            340                 345                 350         


Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Val Pro Thr Ser His 
        355                 360                 365             


Tyr Val Val Asp Val Trp Gly Gln Gly Val Ser Val Thr Val Ser Ser 
    370                 375                 380                 


Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala 
385                 390                 395                 400 


Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
                405                 410                 415     


Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser 
            420                 425                 430         


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 
        435                 440                 445             


Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val 
    450                 455                 460                 


Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 
465                 470                 475                 480 


Ile Val Pro Arg Asp Cys Gly His His His His His His His His His 
                485                 490                 495     


His 
    


<210>  13
<211>  52
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-1 analogue with C-terminal peptidic linker


<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<400>  13

His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Arg Gly Gly 
            20                  25                  30          


Gln Ala Pro Gly Gln Ala Pro Gly Gln Ala Pro Gly Gln Ala Pro Gly 
        35                  40                  45              


Gln Ala Pro Lys 
    50          


<210>  14
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptidic linker

<400>  14

Gly Gln Ala Pro Gly Gln Ala Pro Gly Gln Ala Pro Gly Gln Ala Pro 
1               5                   10                  15      


Gly Gln Ala Pro Lys 
            20      


<210>  15
<211>  31
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-1 analogue

<400>  15

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Arg Glu Phe Ile Ala Trp Leu Val Arg Gly Lys Gly 
            20                  25                  30      


<210>  16
<211>  31
<212>  PRT
<213>  Homo sapiens

<400>  16

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      


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

<220>
<223>  Signal peptide

<400>  17

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 
1               5                   10                  15      


