                         SEQUENCE LISTING

<110>  AMGEN INC.
 
<120>  TREATMENT OF BILE ACID DISORDERS

<130>  A-1943-WO-PCT

<140>  XX/XXX,XXX
<141>  2016-09-20

<150>  62/236,050
<151>  2015-10-01

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  181
<212>  PRT
<213>  Homo sapiens


<220>
<221>  mat_peptide
<222>  (1)..(181)

<400>  1

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>  2
<211>  546
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Human FGF21 DNA

<400>  2
caccccatcc ctgactccag tcctctcctg caattcgggg gccaagtccg gcagcggtac       60

ctctacacag atgatgccca gcagacagaa gcccacctgg agatcaggga ggatgggacg      120

gtggggggcg ctgctgacca gagccccgaa agtctcctgc agctgaaagc cttgaagccg      180

ggagttattc aaatcttggg agtcaagaca tccaggttcc tgtgccagcg gccagatggg      240

gccctgtatg gatcgctcca ctttgaccct gaggcctgca gcttccggga gctgcttctt      300

gaggacggat acaatgttta ccagtccgaa gcccacggcc tcccgctgca cctgccaggg      360

aacaagtccc cacaccggga ccctgcaccc cgaggaccag ctcgcttcct gccactacca      420

ggcctgcccc ccgcactccc ggagccaccc ggaatcctgg ccccccagcc ccccgatgtg      480

ggctcctcgg accctctgag catggtggga ccttcccagg gccgaagccc cagctacgct      540

tcctga                                                                 546


<210>  3
<211>  424
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  AMG 876 Protein

<400>  3

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>  4
<211>  424
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  AMG 875 Protein

<400>  4

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>  5
<211>  15
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  5

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


<210>  6
<211>  15
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  6

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


<210>  7
<211>  8
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  7

Gly Gly Gly Asn Gly Ser Gly Gly 
1               5               


<210>  8
<211>  8
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  8

Gly Gly Gly Asn Gly Ser Gly Gly 
1               5               


<210>  9
<211>  8
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  9

Gly Gly Gly Cys Gly Gly Gly Gly 
1               5               


<210>  10
<211>  5
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  Protein Linker

<400>  10

Gly Pro Asn Gly Gly 
1               5   


<210>  11
<211>  228
<212>  PRT
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  IgG Fc

<400>  11

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 
225             


<210>  12
<211>  208
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Full Length Human FGF21

<400>  12

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 Gly Ala Cys Gln Ala His Pro Ile Pro Asp 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


<210>  13
<211>  627
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Full Length Human FGF21 DNA

<400>  13
atggactcgg acgagaccgg gttcgagcac tcaggactgt gggtttctgt gctggctggt       60

ctgctgggag cctgccaggc acaccccatc cctgactcca gtcctctcct gcaattcggg      120

ggccaagtcc ggcagcggta cctctacaca gatgatgccc agcagacaga agcccacctg      180

gagatcaggg aggatgggac ggtggggggc gctgctgacc agagccccga aagtctcctg      240

cagctgaaag ccttgaagcc gggagttatt caaatcttgg gagtcaagac atccaggttc      300

ctgtgccagc ggccagatgg ggccctgtat ggatcgctcc actttgaccc tgaggcctgc      360

agcttccggg agctgcttct tgaggacgga tacaatgttt accagtccga agcccacggc      420

ctcccgctgc acctgccagg gaacaagtcc ccacaccggg accctgcacc ccgaggacca      480

gctcgcttcc tgccactacc aggcctgccc cccgcactcc cggagccacc cggaatcctg      540

gccccccagc cccccgatgt gggctcctcg gaccctctga gcatggtggg accttcccag      600

ggccgaagcc ccagctacgc ttcctga                                          627


<210>  14
<211>  40
<212>  DNA
<213>  ARTIFICIAL SEQUENCE

<220>
<223>  PCR Primer for Preparing FGF21 Construct

<400>  14
aggaggaata acatatgcat ccaattccag attcttctcc                             40


<210>  15
<211>  33
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  PCR Primer for Preparing FGF21 Construct

<400>  15
tagtgagctc gaattcttag gaagcgtagc tgg                                    33


