                         SEQUENCE LISTING

<110>  BRISTOL-MYERS SQUIBB COMPANY
 
<120>  COMBINATION THERAPY

<130>  3338.227PC05/ELE/C-K/JCA

<150>  US 63/063,189
<151>  2020-08-07  

<150>  US 63/065,414
<151>  2020-08-13

<150>  US 63/065,749 
<151>  2020-08-14

<150>  US 63/065,935
<151>  2020-08-14

<150>  US 63/067,184
<151>  2020-08-18

<160>  19    

<170>  PatentIn version 3.5

<210>  1
<211>  182
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Q109 modified FGF-21


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  Wild-type Q109 replaced with para-acetyl-L-phenylalanine

<400>  1

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


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


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


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


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


Ser Pro Ser Tyr Ala Ser 
            180         


<210>  2
<211>  182
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PEGylated Q109pAF FGF-21


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  poly(ethylene glycol) via oxime linkage

<400>  2

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


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


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


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


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


Ser Pro Ser Tyr Ala Ser 
            180         


<210>  3
<211>  182
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF-21 wild type sequence

<400>  3

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


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


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


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


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


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


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


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


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


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


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


Ser Pro Ser Tyr Ala Ser 
            180         


<210>  4
<211>  182
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PEGylated Q109pAF FGF-21 with 681 unit PEG (PEG681)


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  wherein ON- is the oxime linkage

<400>  4

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


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


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


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


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


Ser Pro Ser Tyr Ala Ser 
            180         


<210>  5
<211>  173
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated Wild-type Q109 replaced with para-acetyl-L-phenylalanine


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  Xaa can be any naturally occurring amino acid

<400>  5

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


His Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe 
        115                 120                 125             


Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile 
    130                 135                 140                 


Leu Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met 
145                 150                 155                 160 


Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170             


<210>  6
<211>  173
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated Para-acetyl-L-phenylalanine linked to a 28-32kDa PEG 
       poly(ethylene glycol) via oxime linkage


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  Xaa can be any naturally occurring amino acid

<400>  6

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


His Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe 
        115                 120                 125             


Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile 
    130                 135                 140                 


Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met 
145                 150                 155                 160 


Val Glu Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170             


<210>  7
<211>  173
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated FGF-21 wild type sequence

<400>  7

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


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


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


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


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


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


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


His Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe 
        115                 120                 125             


Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile 
    130                 135                 140                 


Leu Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met 
145                 150                 155                 160 


Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170             


<210>  8
<211>  173
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated PEGylated Q109pAF FGF-21 with 681 unit PEG (PEG681)


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  Xaa can be any naturally occurring amino acid

<400>  8

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


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


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


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


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


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


Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa Ser Glu Ala 
            100                 105                 110         


His Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe 
        115                 120                 125             


Leu Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile 
    130                 135                 140                 


Leu Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met 
145                 150                 155                 160 


Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170             


<210>  9
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Q108 modified FGF-21


<220>
<221>  misc_feature
<222>  (108)..(108)
<223>  Wild-type Q108 replaced with para-acetyl-L-phenylalanine

<400>  9

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

<220>
<223>  PEGylated Q108pAF FGF-21


<220>
<221>  misc_feature
<222>  (108)..(108)
<223>  poly(ethylene glycol) via oxime linkage

<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 Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa 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>  11
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF-21 wild type sequence

<400>  11

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

<220>
<223>  PEGylated Q108pAF FGF-21 with 681 unit PEG (PEG681)


<220>
<221>  misc_Feature
<222>  (108)..(108)
<223>  wherein ON- is the oxime linkage

<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 Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Xaa 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>  13
<211>  172
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated Wild-type Q108 replaced with para-acetyl-L-phenylalanine


<220>
<221>  misc_Feature
<222>  (108)..(108)
<223>  Xaa can be any naturally occurring amino acid

<400>  13

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 Xaa Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe Leu 
        115                 120                 125             


Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu 
    130                 135                 140                 


Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met Val 
145                 150                 155                 160 


Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170         


<210>  14
<211>  172
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated Para-acetyl-L-phenylalanine linked to a 28-32kDa PEG   

       poly(ethylene glycol) via oxime linkage


<220>
<221>  misc_Feature
<222>  (108)..(108)
<223>  Xaa can be any naturally occurring amino acid

<400>  14

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 Xaa Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Gly Ser Gly Arg Gly Pro Ala Arg Phe Leu 
        115                 120                 125             


Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu 
    130                 135                 140                 


Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val 
145                 150                 155                 160 


Glu Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170         


<210>  15
<211>  172
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated FGF-21 wild type sequence

<400>  15

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 Gly Ser Gly Arg Gly Pro Ala Arg Phe Leu 
        115                 120                 125             


Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu 
    130                 135                 140                 


Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met Val 
145                 150                 155                 160 


Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170         


<210>  16
<211>  172
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mutated PEGylated Q108pAF FGF-21 with 681 unit PEG (PEG681)


<220>
<221>  misc_Feature
<222>  (108)..(108)
<223>  Xaa can be any naturally occurring amino acid

<400>  16

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 Gly Ser Gly Arg Gly Pro Ala Arg Phe Leu 
        115                 120                 125             


Pro Leu Pro Gly Leu Pro Pro Ala Pro Pro Glu Pro Pro Gly Ile Leu 
    130                 135                 140                 


Ala Pro Gln Pro Pro Asp Val Glu Ser Ser Asp Pro Leu Ser Met Val 
145                 150                 155                 160 


Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
                165                 170         


<210>  17
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF-21 variant subsitution

<400>  17

Pro Gly Asn Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly 
1               5                   10                  


<210>  18
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FGF-21 variant subsitution

<400>  18

Gly Ser Gly Arg Gly 
1               5   


<210>  19
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  albumin-binding peptide core sequence

<400>  19

Asp Ile Cys Leu Pro Arg Trp Gly Cys Leu Trp 
1               5                   10      


