                         SEQUENCE LISTING

<110>  Stanislaus, Shanaka
       Xu, Jing
       Ellison, Murielle M.
 
<120>  FGF21 Mutants and Uses Thereof

<130>  A-1651-WO-PCT

<150>  61/529,641
<151>  2011-08-31

<160>  47    

<170>  PatentIn version 3.5

<210>  1
<211>  630
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(630)

<400>  1
atg gac tcg gac gag acc ggg ttc gag cac tca gga ctg tgg gtt tct         48
Met Asp Ser Asp Glu Thr Gly Phe Glu His Ser Gly Leu Trp Val Ser           
1               5                   10                  15                

gtg ctg gct ggt ctt ctg ctg gga gcc tgc cag gca cac ccc atc cct         96
Val Leu Ala Gly Leu Leu Leu Gly Ala Cys Gln Ala His Pro Ile Pro           
            20                  25                  30                    

gac tcc agt cct ctc ctg caa ttc ggg ggc caa gtc cgg cag cgg tac        144
Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr           
        35                  40                  45                        

ctc tac aca gat gat gcc cag cag aca gaa gcc cac ctg gag atc agg        192
Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His Leu Glu Ile Arg           
    50                  55                  60                            

gag gat ggg acg gtg ggg ggc gct gct gac cag agc ccc gaa agt ctc        240
Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu           
65                  70                  75                  80            

ctg cag ctg aaa gcc ttg aag ccg gga gtt att caa atc ttg gga gtc        288
Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val           
                85                  90                  95                

aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg gcc ctg tat gga        336
Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly           
            100                 105                 110                   

tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgg gag ctg ctt ctt        384
Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu           
        115                 120                 125                       

gag gac gga tac aat gtt tac cag tcc gaa gcc cac ggc ctc ccg ctg        432
Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu           
    130                 135                 140                           

cac ctg cca ggg aac aag tcc cca cac cgg gac cct gca ccc cga gga        480
His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly           
145                 150                 155                 160           

cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc gca ccc ccg gag        528
Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu           
                165                 170                 175               

cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg ggc tcc tcg gac        576
Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp           
            180                 185                 190                   

cct ctg agc atg gtg gga cct tcc cag ggc cga agc ccc agc tac gct        624
Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala           
        195                 200                 205                       

tcc tga                                                                630
Ser                                                                       
                                                                          


<210>  2
<211>  209
<212>  PRT
<213>  Homo sapiens

<400>  2

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>  3
<211>  546
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(546)

<400>  3
cac ccc atc cct gac tcc agt cct ctc ctg caa ttc ggg ggc caa gtc         48
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val           
1               5                   10                  15                

cgg cag cgg tac ctc tac aca gat gat gcc cag cag aca gaa gcc cac         96
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His           
            20                  25                  30                    

ctg gag atc agg gag gat ggg acg gtg ggg ggc gct gct gac cag agc        144
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser           
        35                  40                  45                        

ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg gga gtt att caa        192
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln           
    50                  55                  60                            

atc ttg gga gtc aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg        240
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly           
65                  70                  75                  80            

gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgg        288
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg           
                85                  90                  95                

gag ctg ctt ctt gag gac gga tac aat gtt tac cag tcc gaa gcc cac        336
Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His           
            100                 105                 110                   

ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac cgg gac cct        384
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro           
        115                 120                 125                       

gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc        432
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro           
    130                 135                 140                           

gca ccc ccg gag cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg        480
Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val           
145                 150                 155                 160           

ggc tcc tcg gac cct ctg agc atg gtg gga cct tcc cag ggc cga agc        528
Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser           
                165                 170                 175               

ccc agc tac gct tcc tga                                                546
Pro Ser Tyr Ala Ser                                                       
            180                                                           


<210>  4
<211>  181
<212>  PRT
<213>  Homo sapiens

<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 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>  5
<211>  630
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(630)

<400>  5
atg gac tcg gac gag acc ggg ttc gag cac tca gga ctg tgg gtt tct         48
Met Asp Ser Asp Glu Thr Gly Phe Glu His Ser Gly Leu Trp Val Ser           
1               5                   10                  15                

gtg ctg gct ggt ctt ctg ctg gga gcc tgc cag gca cac ccc atc cct         96
Val Leu Ala Gly Leu Leu Leu Gly Ala Cys Gln Ala His Pro Ile Pro           
            20                  25                  30                    

gac tcc agt cct ctc ctg caa ttc ggg ggc caa gtc cgg cag cgg tac        144
Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr           
        35                  40                  45                        

ctc tac aca gat gat gcc cag cag aca gaa gcc cac ctg gag atc agg        192
Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His Leu Glu Ile Arg           
    50                  55                  60                            

gag gat ggg acg gtg ggg ggc gct gct gac cag agc ccc gaa agt ctc        240
Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu           
65                  70                  75                  80            

ctg cag ctg aaa gcc ttg aag ccg gga gtt att caa atc ttg gga gtc        288
Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val           
                85                  90                  95                

aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg gcc ctg tat gga        336
Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly           
            100                 105                 110                   

tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgg gag ctg ctt ctt        384
Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu           
        115                 120                 125                       

gag gac gga tac aat gtt tac cag tcc gaa gcc cac ggc ctc ccg ctg        432
Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu           
    130                 135                 140                           

cac ctg cca ggg aac aag tcc cca cac cgg gac cct gca ccc cga gga        480
His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly           
145                 150                 155                 160           

cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc gca ctc ccg gag        528
Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Leu Pro Glu           
                165                 170                 175               

cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg ggc tcc tcg gac        576
Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp           
            180                 185                 190                   

cct ctg agc atg gtg gga cct tcc cag ggc cga agc ccc agc tac gct        624
Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala           
        195                 200                 205                       

tcc tga                                                                630
Ser                                                                       
                                                                          


<210>  6
<211>  209
<212>  PRT
<213>  Homo sapiens

<400>  6

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 Leu 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>  7
<211>  546
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(546)

<400>  7
cac ccc atc cct gac tcc agt cct ctc ctg caa ttc ggg ggc caa gtc         48
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val           
1               5                   10                  15                

cgg cag cgg tac ctc tac aca gat gat gcc cag cag aca gaa gcc cac         96
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His           
            20                  25                  30                    

ctg gag atc agg gag gat ggg acg gtg ggg ggc gct gct gac cag agc        144
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser           
        35                  40                  45                        

ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg gga gtt att caa        192
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln           
    50                  55                  60                            

atc ttg gga gtc aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg        240
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly           
65                  70                  75                  80            

gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgg        288
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg           
                85                  90                  95                

gag ctg ctt ctt gag gac gga tac aat gtt tac cag tcc gaa gcc cac        336
Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His           
            100                 105                 110                   

ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac cgg gac cct        384
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro           
        115                 120                 125                       

gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc        432
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro           
    130                 135                 140                           

gca ctc ccg gag cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg        480
Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val           
145                 150                 155                 160           

ggc tcc tcg gac cct ctg agc atg gtg gga cct tcc cag ggc cga agc        528
Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser           
                165                 170                 175               

ccc agc tac gct tcc tga                                                546
Pro Ser Tyr Ala Ser                                                       
            180                                                           


<210>  8
<211>  181
<212>  PRT
<213>  Homo sapiens

<400>  8

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 Leu 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>  9
<211>  543
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Human FGF21 L98R P171G


<220>
<221>  CDS
<222>  (1)..(543)

<400>  9
cat cca att cca gat tct tct cca tta tta caa ttc ggg ggc caa gtc         48
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val           
1               5                   10                  15                

cgg cag cgt tac ctc tac aca gat gat gcc cag cag aca gaa gcc cac         96
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His           
            20                  25                  30                    

ctg gag atc agg gag gac ggg acg gtg ggg ggt gct gct gac cag agc        144
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser           
        35                  40                  45                        

ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg ggt gtt att caa        192
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln           
    50                  55                  60                            

atc ttg ggt gtc aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg        240
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly           
65                  70                  75                  80            

gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgt        288
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg           
                85                  90                  95                

gag cgt ctt ctt gag gac ggt tac aat gtt tac cag tcc gaa gcc cac        336
Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His           
            100                 105                 110                   

ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac cgt gac cct        384
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro           
        115                 120                 125                       

gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc        432
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro           
    130                 135                 140                           

gca ccc ccg gag cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg        480
Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val           
145                 150                 155                 160           

ggc tcc tcg gac cct ctg agc atg gtg ggt ggt tcc cag ggc cga agc        528
Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln Gly Arg Ser           
                165                 170                 175               

ccc agc tac gct tcc                                                    543
Pro Ser Tyr Ala Ser                                                       
            180                                                           


<210>  10
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  10

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 Arg 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 Gly Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  11
<211>  543
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Human FGF21 L98R P171G A180E Variant


<220>
<221>  CDS
<222>  (1)..(543)

<400>  11
cat cca att cca gat tct tct cca tta tta caa ttc ggg ggc caa gtc         48
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val           
1               5                   10                  15                

cgg cag cgt tac ctc tac aca gat gat gcc cag cag aca gaa gcc cac         96
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His           
            20                  25                  30                    

ctg gag atc agg gag gac ggg acg gtg ggg ggt gct gct gac cag agc        144
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser           
        35                  40                  45                        

ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg ggt gtt att caa        192
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln           
    50                  55                  60                            

atc ttg ggt gtc aag aca tcc agg ttc ctg tgc cag cgg cca gat ggg        240
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly           
65                  70                  75                  80            

gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc agc ttc cgt        288
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg           
                85                  90                  95                

gag cgt ctt ctt gag gac ggt tac aat gtt tac cag tcc gaa gcc cac        336
Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His           
            100                 105                 110                   

ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac cgt gac cct        384
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro           
        115                 120                 125                       

gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc ctg ccc ccc        432
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro           
    130                 135                 140                           

gca ccc ccg gag cca ccc gga atc ctg gcc ccc cag ccc ccc gat gtg        480
Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val           
145                 150                 155                 160           

ggc tcc tcg gac cct ctg agc atg gtg ggt ggt tcc cag ggc cga agc        528
Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln Gly Arg Ser           
                165                 170                 175               

ccc agc tac gaa tcc                                                    543
Pro Ser Tyr Glu Ser                                                       
            180                                                           


<210>  12
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  12

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 Arg 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 Gly Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Glu Ser 
            180     


<210>  13
<211>  4
<212>  PRT
<213>  Artificial

<220>
<223>  G4 Linker

<400>  13

Gly Gly Gly Gly 
1               


<210>  14
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  G5 Linker

<400>  14

Gly Gly Gly Gly Gly 
1               5   


<210>  15
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  15

Gly Gly Gly Gly Ser 
1               5   


<210>  16
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G4S)2 Linker

<400>  16

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


<210>  17
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  17

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


Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            20                  25  


<210>  18
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  18

Gly Gly Glu Gly Gly Gly 
1               5       


<210>  19
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  19

Gly Gly Glu Glu Glu Gly Gly Gly 
1               5               


<210>  20
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  20

Gly Glu Glu Glu Gly 
1               5   


<210>  21
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  21

Gly Glu Glu Glu 
1               


<210>  22
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  22

Gly Gly Asp Gly Gly Gly 
1               5       


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

<220>
<223>  synthesized linker

<400>  23

Gly Gly Asp Asp Asp Gly Gly 
1               5           


<210>  24
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  24

Gly Asp Asp Asp Gly 
1               5   


<210>  25
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  25

Gly Asp Asp Asp 
1               


<210>  26
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  26

Gly Gly Gly Gly Ser Asp Asp Ser Asp Glu Gly Ser Asp Gly Glu Asp 
1               5                   10                  15      


Gly Gly Gly Gly Ser 
            20      


<210>  27
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  27

Trp Glu Trp Glu Trp 
1               5   


<210>  28
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  28

Phe Glu Phe Glu Phe 
1               5   


<210>  29
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  29

Glu Glu Glu Trp Trp Trp 
1               5       


<210>  30
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  30

Glu Glu Glu Phe Phe Phe 
1               5       


<210>  31
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  31

Trp Trp Glu Glu Glu Trp Trp 
1               5           


<210>  32
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthesized linker

<400>  32

Phe Phe Glu Glu Glu Phe Phe 
1               5           


<210>  33
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  (G4S)3 Linker

<400>  33

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


<210>  34
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  G3KG4 linker

<400>  34

Gly Gly Gly Lys Gly Gly Gly Gly 
1               5               


<210>  35
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  G3NGSG2 Linker

<400>  35

Gly Gly Gly Asn Gly Ser Gly Gly 
1               5               


<210>  36
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  G3CG4 linker

<400>  36

Gly Gly Gly Cys Gly Gly Gly Gly 
1               5               


<210>  37
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  GPNG2 Linker

<400>  37

Gly Pro Asn Gly Gly 
1               5   


<210>  38
<211>  1275
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fc-(G4S)3-RG


<220>
<221>  CDS
<222>  (1)..(1275)

<400>  38
atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc ctg         48
Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu           
1               5                   10                  15                

ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc ctc         96
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu           
            20                  25                  30                    

atg atc tcc cgt acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc        144
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser           
        35                  40                  45                        

cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag        192
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu           
    50                  55                  60                            

gtg cat aat gcc aag aca aag ccg cgt gag gag cag tac aac agc acg        240
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr           
65                  70                  75                  80            

tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat        288
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn           
                85                  90                  95                

ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc        336
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro           
            100                 105                 110                   

atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag        384
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln           
        115                 120                 125                       

gtg tac acc ctg ccc cca tcc cgt gat gag ctg acc aag aac cag gtc        432
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val           
    130                 135                 140                           

agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg        480
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val           
145                 150                 155                 160           

gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg cct        528
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro           
                165                 170                 175               

ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc        576
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr           
            180                 185                 190                   

gtg gac aag agc cgt tgg cag cag ggg aac gtc ttc tca tgc tcc gtg        624
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val           
        195                 200                 205                       

atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc ctg        672
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu           
    210                 215                 220                           

tct ccg ggt aaa ggt ggt ggt ggt tcc ggt ggc ggc ggc tct ggt ggt        720
Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly           
225                 230                 235                 240           

ggt ggc agc cat ccg atc ccg gac tct tct ccg ctg ctg cag ttc ggt        768
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly           
                245                 250                 255               

ggt cag gtt cgt cag cgt tac ctg tac acc gac gac gcg cag cag acc        816
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr           
            260                 265                 270                   

gag gcg cac ctg gag atc cgt gaa gac ggt acc gtt ggt ggt gcg gcc        864
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala           
        275                 280                 285                       

gac cag tct ccg gaa tct ctg ctg cag ctg aaa gcc ctg aaa ccg ggt        912
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly           
    290                 295                 300                           

gtt atc cag atc ctg ggc gtt aaa acc tct cgt ttc ctg tgc cag cgt        960
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg           
305                 310                 315                 320           

ccg gac ggc gcc ctg tac ggt tct ctg cac ttc gac ccg gag gcg tgc       1008
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys           
                325                 330                 335               

tct ttt cgt gaa cgt ctg ctc gaa gac ggt tac aac gtt tac cag tct       1056
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser           
            340                 345                 350                   

gag gcg cac ggt ctg ccg ctg cac ctg ccg ggt aac aaa tct ccg cac       1104
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His           
        355                 360                 365                       

cgt gac ccg gcg cca cgt ggt cct gcg cgt ttc ctg cca ctg ccg ggc       1152
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly           
    370                 375                 380                           

ctg ccg cct gcg cct cct gaa ccg cct ggt atc ctg gct ccg cag ccg       1200
Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro           
385                 390                 395                 400           

cca gac gtt ggt tct tct gac ccg ctg tct atg gtt ggt ggc tct cag       1248
Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln           
                405                 410                 415               

ggt cgt tct ccg tct tac gcc tct taa                                   1275
Gly Arg Ser Pro Ser Tyr Ala Ser                                           
            420                                                           


<210>  39
<211>  424
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  39

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     


Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         


Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             


Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 


Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 


Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     


Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         


Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             


Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 


Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 


Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln 
                405                 410                 415     


Gly Arg Ser Pro Ser Tyr Ala Ser 
            420                 


<210>  40
<211>  1275
<212>  DNA
<213>  Artificial

<220>
<223>  Fc-(G4S)3-RGE


<220>
<221>  CDS
<222>  (1)..(1275)

<400>  40
atg gac aaa act cac aca tgt cca cct tgt cca gct ccg gaa ctc ctg         48
Met Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu           
1               5                   10                  15                

ggg gga ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc ctc         96
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu           
            20                  25                  30                    

atg atc tcc cgt acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc        144
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser           
        35                  40                  45                        

cac gaa gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag        192
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu           
    50                  55                  60                            

gtg cat aat gcc aag aca aag ccg cgt gag gag cag tac aac agc acg        240
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr           
65                  70                  75                  80            

tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat        288
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn           
                85                  90                  95                

ggc aag gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc        336
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro           
            100                 105                 110                   

atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag        384
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln           
        115                 120                 125                       

gtg tac acc ctg ccc cca tcc cgt gat gag ctg acc aag aac cag gtc        432
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val           
    130                 135                 140                           

agc ctg acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg        480
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val           
145                 150                 155                 160           

gag tgg gag agc aat ggg cag ccg gag aac aac tac aag acc acg cct        528
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro           
                165                 170                 175               

ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc        576
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr           
            180                 185                 190                   

gtg gac aag agc cgt tgg cag cag ggg aac gtc ttc tca tgc tcc gtg        624
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val           
        195                 200                 205                       

atg cat gag gct ctg cac aac cac tac acg cag aag agc ctc tcc ctg        672
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu           
    210                 215                 220                           

tct ccg ggt aaa ggt ggt ggt ggt tct ggt ggt ggt ggt agc ggt ggt        720
Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly           
225                 230                 235                 240           

ggt ggt tcc cat cca att cca gat tct tct cca tta tta caa ttc ggg        768
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly           
                245                 250                 255               

ggc caa gtc cgg cag cgt tac ctc tac aca gat gat gcc cag cag aca        816
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr           
            260                 265                 270                   

gaa gcc cac ctg gag atc agg gag gac ggg acg gtg ggg ggt gct gct        864
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala           
        275                 280                 285                       

gac cag agc ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg ggt        912
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly           
    290                 295                 300                           

gtt att caa atc ttg ggt gtc aag aca tcc agg ttc ctg tgc cag cgg        960
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg           
305                 310                 315                 320           

cca gat ggg gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc       1008
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys           
                325                 330                 335               

agc ttc cgt gag cgt ctt ctt gag gac ggt tac aat gtt tac cag tcc       1056
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser           
            340                 345                 350                   

gaa gcc cac ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac       1104
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His           
        355                 360                 365                       

cgt gac cct gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc       1152
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly           
    370                 375                 380                           

ctg ccc ccc gca ccc ccg gag cca ccc gga atc ctg gcc ccc cag ccc       1200
Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro           
385                 390                 395                 400           

ccc gat gtg ggc tcc tcg gac cct ctg agc atg gtg ggt ggt tcc cag       1248
Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln           
                405                 410                 415               

ggc cga agc ccc agc tac gaa tcc taa                                   1275
Gly Arg Ser Pro Ser Tyr Glu Ser                                           
            420                                                           


<210>  41
<211>  424
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic Construct

<400>  41

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 


Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     


Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         


Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             


Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 


Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 


Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     


Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         


Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             


Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 


Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 


Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln 
                405                 410                 415     


Gly Arg Ser Pro Ser Tyr Glu Ser 
            420                 


<210>  42
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  (G4S)4 Linker

<400>  42

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


Gly Gly Gly Ser 
            20  


<210>  43
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial Peptidyl Linker Sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  X3 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X4 is any amino acid

<400>  43

Xaa Xaa Tyr Xaa Xaa 
1               5   


<210>  44
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial Peptidyl Linker Sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  X3 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X4 is any amino acid

<400>  44

Xaa Xaa Ser Xaa Xaa Gly 
1               5       


<210>  45
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial Peptidyl Linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  X3 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X4 is any amino acid

<400>  45

Xaa Xaa Thr Xaa Xaa Gly 
1               5       


<210>  46
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  XXNXXG Linker Sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  X3 is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X4 is any amino acid

<400>  46

Xaa Xaa Asn Xaa Xaa Gly 
1               5       


<210>  47
<211>  230
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG4 Fc


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xas is A or absent

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xas is S or P

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xas is P or E

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xas is F, V or A

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xas is L, E or A

<220>
<221>  MISC_FEATURE
<222>  (80)..(80)
<223>  Xas is N or A

<220>
<221>  MISC_FEATURE
<222>  (230)..(230)
<223>  Xas is K or absent

<400>  47

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


Xaa Xaa Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Leu Gly Xaa 
225                 230 


