                         SEQUENCE LISTING

<110>  SANOFI
 
<120>  FGF21 compound / GLP-1R agonist combinations with optimized 
       activity ratio

<130>  589-264 PCT

<150>  EP 16 306 776.2
<151>  December 22, 2016

<160>  43    

<170>  PatentIn version 3.5

<210>  1
<211>  209
<212>  PRT
<213>  Homo sapiens

<400>  1

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


Val Leu Ala Gly Leu Leu Leu Gly Ala Cys Gln Ala His Pro Ile Pro 
            20                  25                  30          


Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr 
        35                  40                  45              


Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His Leu Glu Ile Arg 
    50                  55                  60                  


Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu 
65                  70                  75                  80  


Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val 
                85                  90                  95      


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


Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu 
        115                 120                 125             


Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu 
    130                 135                 140                 


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


Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu 
                165                 170                 175     


Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp 
            180                 185                 190         


Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala 
        195                 200                 205             


Ser 
    


<210>  2
<211>  181
<212>  PRT
<213>  Homo sapiens

<400>  2

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  3
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF21(His29-Ser209) A59C,G71C

<400>  3

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Cys His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Cys Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  4
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF21(His29-Ser209) Q55C,N149C,G198Y

<400>  4

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Tyr Pro Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  5
<211>  180
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF21(His29-Ser209) Q55C,P147C,delP199

<400>  5

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Cys Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser Gln Gly Arg Ser Pro 
                165                 170                 175     


Ser Tyr Ala Ser 
            180 


<210>  6
<211>  180
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF21(His29-Ser209) Q55C,N149C,delP199

<400>  6

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser Gln Gly Arg Ser Pro 
                165                 170                 175     


Ser Tyr Ala Ser 
            180 


<210>  7
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  7

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 
            20                  25                  30  


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

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,L20M,G22E,Q23E,A25V,K26R,E27L,A30E,V33K,K34N,R
       36G,insPSSGAPPPS

<400>  8

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  9
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G,insPSSGAPPPS

<400>  9

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  10
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18I,Y19Q,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,G
       35T,R36G,insPVSGAPPPS

<400>  10

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Asp Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  11
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18I,Y19Q,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33E,K34A,G
       35T,R36G,insPVSGAPPPS

<400>  11

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Asp Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  12
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,R
       36G,insPSSGAPPPS

<400>  12

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser 
        35                  40  


<210>  13
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,G
       35T,R36G,insPSSGAPPPS

<400>  13

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser 
        35                  40  


<210>  14
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,E21D,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G
       35T,R36G,insPSSGEPPPES

<400>  14

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Glu Pro Pro Pro Glu Ser 
        35                  40  


<210>  15
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,L20M,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33K,K
       34N,R36G

<400>  15

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu 
1               5                   10                  15      


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


<210>  16
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G

<400>  16

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


<210>  17
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G,insPSSGEPPPE

<400>  17

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Glu Pro Pro Pro Glu 
        35                  


<210>  18
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18K,Y19Q,G22E,Q23E,A24R,A25V,K26Q,A30E,insPSSGAPPP
       S

<400>  18

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser 
        35                  40  


<210>  19
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33E,K34A,G35T,R
       36G,insPSSGAPPPS

<400>  19

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  20
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,R
       36G,insPKKQRLS

<400>  20

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Lys Lys Gln Arg Leu Ser 
        35              


<210>  21
<211>  228
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG4 Fc variant, IGHG4_HUMAN (Glu99-Gly326)

<400>  21

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


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


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


Leu Ser Leu Gly 
225             


<210>  22
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G7S)(G4S)(G4S)A Linker (19GS)

<400>  22

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


Gly Ser Ala 
            


<210>  23
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G3S)(GS)A Linker (7GS)

<400>  23

Gly Gly Gly Ser Gly Ser Ala 
1               5           


<210>  24
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36)  
       A8G,V16L,S18K,Y19Q,L20M,G22E,Q23E,A25V,K26R,E27L,A30E,V33K,K34N,R
       36G,insPSSGAPPPS_[19GS]_IgG4 Fc_variant [7GS]_ 
       FGF21(His29-Ser209)_A59C,G71C

<400>  24

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln 
305                 310                 315                 320 


Gln Thr Glu Cys His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Cys 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  25
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G,insPSSGAPPPS_[19GS] _IgG4 Fc 
       variant_[7GS]_FGF21(His29-Ser209)Q55C,N149C,G198Y

<400>  25

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys 
305                 310                 315                 320 


Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Tyr Pro 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  26
<211>  473
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18I,Y19Q,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,G
       35T,R36G,insPVSGAPPPS_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,P147C,delP199

<400>  26

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Asp Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys 
305                 310                 315                 320 


Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Cys Gly Asn Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser 
    450                 455                 460                 


Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470             


<210>  27
<211>  473
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18I,Y19Q,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33E,K34A,G
       35T,R36G,insPVSGAPPPS_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,delP199

<400>  27

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Asp Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys 
305                 310                 315                 320 


Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser 
    450                 455                 460                 


Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470             


<210>  28
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,R
       36G,insPSSGAPPPS_[19GS] _IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,delP199

<400>  28

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser 
        35                  40                  45              


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly 
    50                  55                  60                  


Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser 
65                  70                  75                  80  


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                85                  90                  95      


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        115                 120                 125             


Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
    130                 135                 140                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
145                 150                 155                 160 


Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
                165                 170                 175     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            180                 185                 190         


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        195                 200                 205             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    210                 215                 220                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
225                 230                 235                 240 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
                245                 250                 255     


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            260                 265                 270         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly 
        275                 280                 285             


Gly Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu 
    290                 295                 300                 


Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala 
305                 310                 315                 320 


Cys Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly 
                325                 330                 335     


Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu 
            340                 345                 350         


Lys Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu 
        355                 360                 365             


Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro 
    370                 375                 380                 


Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val 
385                 390                 395                 400 


Tyr Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys 
                405                 410                 415     


Ser Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro 
            420                 425                 430         


Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala 
        435                 440                 445             


Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  29
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,G
       35T,R36G,insPSSGAPPPS_[19GS]_Ig4G Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,P147C,delP199

<400>  29

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser 
        35                  40                  45              


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly 
    50                  55                  60                  


Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser 
65                  70                  75                  80  


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                85                  90                  95      


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        115                 120                 125             


Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
    130                 135                 140                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
145                 150                 155                 160 


Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
                165                 170                 175     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            180                 185                 190         


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        195                 200                 205             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    210                 215                 220                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
225                 230                 235                 240 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
                245                 250                 255     


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            260                 265                 270         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly 
        275                 280                 285             


Gly Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu 
    290                 295                 300                 


Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala 
305                 310                 315                 320 


Cys Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly 
                325                 330                 335     


Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu 
            340                 345                 350         


Lys Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu 
        355                 360                 365             


Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro 
    370                 375                 380                 


Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val 
385                 390                 395                 400 


Tyr Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Cys Gly Asn Lys 
                405                 410                 415     


Ser Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro 
            420                 425                 430         


Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala 
        435                 440                 445             


Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  30
<211>  475
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,E21D,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G
       35T,R36G,insPSSGEPPPES_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,G198Y

<400>  30

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Glu Pro Pro Pro Glu Ser Gly Gly Gly Gly Gly Gly Gly Ser 
        35                  40                  45              


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly 
    50                  55                  60                  


Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser 
65                  70                  75                  80  


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                85                  90                  95      


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        115                 120                 125             


Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
    130                 135                 140                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
145                 150                 155                 160 


Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
                165                 170                 175     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            180                 185                 190         


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        195                 200                 205             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    210                 215                 220                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
225                 230                 235                 240 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
                245                 250                 255     


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            260                 265                 270         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly 
        275                 280                 285             


Gly Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu 
    290                 295                 300                 


Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala 
305                 310                 315                 320 


Cys Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly 
                325                 330                 335     


Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu 
            340                 345                 350         


Lys Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu 
        355                 360                 365             


Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro 
    370                 375                 380                 


Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val 
385                 390                 395                 400 


Tyr Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys 
                405                 410                 415     


Ser Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro 
            420                 425                 430         


Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala 
        435                 440                 445             


Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Tyr 
    450                 455                 460                 


Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 475 


<210>  31
<211>  465
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,L20M,E21D,G22E,Q23E,A25V,K26R,E27L,A30E,V33K,K
       34N,R36G_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,G198Y

<400>  31

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu 
1               5                   10                  15      


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


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


Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 
    50                  55                  60                  


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


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                85                  90                  95      


Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 
            100                 105                 110         


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 
        115                 120                 125             


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
    130                 135                 140                 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 
145                 150                 155                 160 


Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                165                 170                 175     


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


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        195                 200                 205             


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    210                 215                 220                 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
225                 230                 235                 240 


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            260                 265                 270         


Ser Leu Ser Leu Gly Gly Gly Gly Ser Gly Ser Ala His Pro Ile Pro 
        275                 280                 285             


Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr 
    290                 295                 300                 


Leu Tyr Thr Asp Asp Ala Cys Gln Thr Glu Ala His Leu Glu Ile Arg 
305                 310                 315                 320 


Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu 
                325                 330                 335     


Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val 
            340                 345                 350         


Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly 
        355                 360                 365             


Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu 
    370                 375                 380                 


Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu 
385                 390                 395                 400 


His Leu Pro Gly Cys Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly 
                405                 410                 415     


Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu 
            420                 425                 430         


Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp 
        435                 440                 445             


Pro Leu Ser Met Val Tyr Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala 
    450                 455                 460                 


Ser 
465 


<210>  32
<211>  465
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G_[19GS]_IgG4 Fc_variant [7GS] 
       FGF21(His29-Ser209)Q55C,N149C,G198Y

<400>  32

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


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


Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 
    50                  55                  60                  


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


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                85                  90                  95      


Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 
            100                 105                 110         


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 
        115                 120                 125             


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
    130                 135                 140                 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 
145                 150                 155                 160 


Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                165                 170                 175     


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


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
        195                 200                 205             


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
    210                 215                 220                 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
225                 230                 235                 240 


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
            260                 265                 270         


Ser Leu Ser Leu Gly Gly Gly Gly Ser Gly Ser Ala His Pro Ile Pro 
        275                 280                 285             


Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr 
    290                 295                 300                 


Leu Tyr Thr Asp Asp Ala Cys Gln Thr Glu Ala His Leu Glu Ile Arg 
305                 310                 315                 320 


Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu 
                325                 330                 335     


Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val 
            340                 345                 350         


Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly 
        355                 360                 365             


Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu 
    370                 375                 380                 


Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu 
385                 390                 395                 400 


His Leu Pro Gly Cys Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly 
                405                 410                 415     


Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu 
            420                 425                 430         


Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp 
        435                 440                 445             


Pro Leu Ser Met Val Tyr Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala 
    450                 455                 460                 


Ser 
465 


<210>  33
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33L,K34A,G35T,R
       36G,insPSSGEPPPE_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,G198Y

<400>  33

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Glu Pro Pro Pro Glu Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys 
305                 310                 315                 320 


Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Tyr Pro 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  34
<211>  474
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18K,Y19Q,G22E,Q23E,A24R,A25V,K26Q,A30E,insPSSGAPPP
       S_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,delP199

<400>  34

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu 
1               5                   10                  15      


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


Ser Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser 
        35                  40                  45              


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly 
    50                  55                  60                  


Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser 
65                  70                  75                  80  


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                85                  90                  95      


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        115                 120                 125             


Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
    130                 135                 140                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
145                 150                 155                 160 


Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
                165                 170                 175     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            180                 185                 190         


Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        195                 200                 205             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    210                 215                 220                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
225                 230                 235                 240 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
                245                 250                 255     


Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            260                 265                 270         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly 
        275                 280                 285             


Gly Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu 
    290                 295                 300                 


Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala 
305                 310                 315                 320 


Cys Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly 
                325                 330                 335     


Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu 
            340                 345                 350         


Lys Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu 
        355                 360                 365             


Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro 
    370                 375                 380                 


Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val 
385                 390                 395                 400 


Tyr Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys 
                405                 410                 415     


Ser Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro 
            420                 425                 430         


Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala 
        435                 440                 445             


Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly 
    450                 455                 460                 


Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470                 


<210>  35
<211>  473
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       A8G,V16L,S18K,Y19Q,G22E,Q23E,A25V,K26Q,E27L,A30E,V33E,K34A,G35T,R
       36G,insPSSGAPPPS_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,delP199

<400>  35

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Leu Glu Glu 
1               5                   10                  15      


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


Ser Gly Ala Pro Pro Pro Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro 
    50                  55                  60                  


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
65                  70                  75                  80  


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                85                  90                  95      


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            100                 105                 110         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        115                 120                 125             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    130                 135                 140                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
145                 150                 155                 160 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                165                 170                 175     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            180                 185                 190         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        195                 200                 205             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    210                 215                 220                 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                245                 250                 255     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            260                 265                 270         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly 
        275                 280                 285             


Gly Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln 
    290                 295                 300                 


Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys 
305                 310                 315                 320 


Gln Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly 
                325                 330                 335     


Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys 
            340                 345                 350         


Pro Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys 
        355                 360                 365             


Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu 
    370                 375                 380                 


Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr 
385                 390                 395                 400 


Gln Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser 
                405                 410                 415     


Pro His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu 
            420                 425                 430         


Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro 
        435                 440                 445             


Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser 
    450                 455                 460                 


Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470             


<210>  36
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP1(7-36) 
       insG,A8G,V16L,S18I,Y19Q,G22E,Q23E,A25V,K26R,E27L,A30E,V33L,K34A,R
       36G,insPKKQRLS_[19GS]_IgG4 Fc_variant 
       [7GS]_FGF21(His29-Ser209)Q55C,N149C,delP199

<400>  36

Gly His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Ile Gln Leu Glu 
1               5                   10                  15      


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


Lys Lys Gln Arg Leu Ser Gly Gly Gly Gly Gly Gly Gly Ser Gly Gly 
        35                  40                  45              


Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu Ser Lys Tyr Gly Pro Pro 
    50                  55                  60                  


Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe 
65                  70                  75                  80  


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                85                  90                  95      


Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val 
            100                 105                 110         


Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
        115                 120                 125             


Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val 
    130                 135                 140                 


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
145                 150                 155                 160 


Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser 
                165                 170                 175     


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


Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        195                 200                 205             


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
    210                 215                 220                 


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


Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp 
                245                 250                 255     


Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            260                 265                 270         


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly 
        275                 280                 285             


Ser Gly Ser Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe 
    290                 295                 300                 


Gly Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Cys Gln 
305                 310                 315                 320 


Thr Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala 
                325                 330                 335     


Ala Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro 
            340                 345                 350         


Gly Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln 
        355                 360                 365             


Arg Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala 
    370                 375                 380                 


Cys Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln 
385                 390                 395                 400 


Ser Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Cys Lys Ser Pro 
                405                 410                 415     


His Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro 
            420                 425                 430         


Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln 
        435                 440                 445             


Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ser Gln 
    450                 455                 460                 


Gly Arg Ser Pro Ser Tyr Ala Ser 
465                 470         


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

<220>
<223>  GLP-1RA, general sequence


<220>
<221>  misc_feature
<222>  (10)..(10)
<223>  Xaa is any amino acid, e.g., L or K

<220>
<221>  misc_feature
<222>  (12)..(12)
<223>  Xaa is any amino acid, e.g., K or I

<220>
<221>  misc_feature
<222>  (14)..(14)
<223>  Xaa is any amino acid, e.g., L or M

<220>
<221>  misc_feature
<222>  (15)..(15)
<223>  Xaa is any amino acid, e.g., E or D

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa is any amino acid, e.g., A or R

<220>
<221>  misc_feature
<222>  (20)..(20)
<223>  Xaa is any amino acid, e.g., R or Q

<220>
<221>  misc_feature
<222>  (21)..(21)
<223>  Xaa is any amino acid, e.g., L or E

<220>
<221>  misc_feature
<222>  (27)..(27)
<223>  Xaa is any amino acid, e.g., L, E, K or V

<220>
<221>  misc_feature
<222>  (28)..(28)
<223>  Xaa is any amino acid, e.g., A, N or K

<220>
<221>  misc_feature
<222>  (29)..(29)
<223>  Xaa is any amino acid, e.g., T or G

<220>
<221>  misc_feature
<222>  (30)..(30)
<223>  Xaa is any amino acid, e.g., G or R

<400>  37

His Gly Glu Gly Thr Phe Thr Ser Asp Xaa Ser Xaa Gln Xaa Xaa Glu 
1               5                   10                  15      


Glu Xaa Val Xaa Xaa Phe Ile Glu Trp Leu Xaa Xaa Xaa Xaa 
            20                  25                  30  


<210>  38
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension I

<400>  38

Pro Ser Ser Gly Ala Pro Pro Pro Ser 
1               5                   


<210>  39
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension II

<400>  39

Pro Val Ser Gly Ala Pro Pro Pro Ser 
1               5                   


<210>  40
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension III

<400>  40

Pro Ser Ser Gly Glu Pro Pro Pro Glu Ser 
1               5                   10  


<210>  41
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension IV

<400>  41

Pro Ser Ser Gly Glu Pro Pro Pro Glu 
1               5                   


<210>  42
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension V

<400>  42

Pro Lys Lys Gln Arg Leu Ser 
1               5           


<210>  43
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal peptide extension VI

<400>  43

Pro Lys Lys Ile Arg Tyr Ser 
1               5           


