                         SEQUENCE LISTING

<110>  AKSTON BIOSCIENCES CORPORATION
 
<120>  ULTRA-LONG ACTING INSULIN-FC FUSION PROTEINS AND METHODS OF USE

<130>  ABC-038US

<160>  100   

<170>  PatentIn version 3.5

<210>  1
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human insulin B-chain

<400>  1

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr 
            20                  25                  30  


<210>  2
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human insulin A-chain

<400>  2

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Tyr Cys Asn 
            20      


<210>  3
<211>  86
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human ProInsulin

<400>  3

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr Arg Arg 
            20                  25                  30          


Glu Ala Glu Asp Leu Gln Val Gly Gln Val Glu Leu Gly Gly Gly Pro 
        35                  40                  45              


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


Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln 
65                  70                  75                  80  


Leu Glu Asn Tyr Cys Asn 
                85      


<210>  4
<211>  57
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide

<400>  4

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
    50                  55          


<210>  5
<211>  58
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide


<220>
<221>  Xaa
<222>  (10)..(10)
<223>  Xaa is not D

<220>
<221>  Xaa
<222>  (45)..(45)
<223>  Xaa is not H

<220>
<221>  Xaa
<222>  (58)..(58)
<223>  Xaa is absent or N

<400>  5

Phe Val Asn Gln His Leu Cys Gly Ser Xaa Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Xaa Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Xaa 
    50                  55              


<210>  6
<211>  58
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide


<220>
<221>  Xaa
<222>  (58)..(58)
<223>  Xaa is absent or N

<400>  6

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Xaa 
    50                  55              


<210>  7
<211>  57
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide

<400>  7

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys 
    50                  55          


<210>  8
<211>  58
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide

<400>  8

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Asn 
    50                  55              


<210>  9
<211>  57
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide


<220>
<221>  Xaa
<222>  (10)..(10)
<223>  Xaa is not D

<220>
<221>  Xaa
<222>  (45)..(45)
<223>  Xaa is not H

<400>  9

Phe Val Asn Gln His Leu Cys Gly Ser Xaa Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Xaa Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys 
    50                  55          


<210>  10
<211>  57
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide

<400>  10

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys 
    50                  55          


<210>  11
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  11

Gly Gly Gly Gly Ala Gly Gly Gly Gly 
1               5                   


<210>  12
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  12

Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   


<210>  13
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  13

Gly Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln 
1               5                   10                  15      


Gly Gly Gly Gly Gly 
            20      


<210>  14
<211>  228
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment dIgGA

<400>  14

Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu Gly Gly 
1               5                   10                  15      


Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg Ile 
            20                  25                  30          


Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg Glu 
        35                  40                  45              


Asp Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His 
    50                  55                  60                  


Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr Arg 
65                  70                  75                  80  


Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly Lys 
                85                  90                  95      


Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile Glu 
            100                 105                 110         


Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val Tyr 
        115                 120                 125             


Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Ser 
    130                 135                 140                 


Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val Glu 
145                 150                 155                 160 


Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met Thr 
                165                 170                 175     


Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         


Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys Ala 
        195                 200                 205             


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


His Ser Pro Gly 
225             


<210>  15
<211>  224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment dIgGB

<400>  15

Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val 
1               5                   10                  15      


Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr 
            20                  25                  30          


Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu 
        35                  40                  45              


Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys 
    50                  55                  60                  


Thr Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr 
                85                  90                  95      


Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile 
            100                 105                 110         


Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro 
        115                 120                 125             


Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu 
    130                 135                 140                 


Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn 
145                 150                 155                 160 


Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu 
                165                 170                 175     


Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys 
            180                 185                 190         


Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu 
        195                 200                 205             


Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    210                 215                 220                 


<210>  16
<211>  225
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment dIgGC

<400>  16

Cys Asn Asn Cys Pro Cys Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser 
1               5                   10                  15      


Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Val Thr Ala Arg 
            20                  25                  30          


Thr Pro Thr Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asn Pro 
        35                  40                  45              


Glu Val Gln Ile Ser Trp Phe Val Asp Ser Lys Gln Val Gln Thr Ala 
    50                  55                  60                  


Asn Thr Gln Pro Arg Glu Glu Gln Ser Asn Gly Thr Tyr Arg Val Val 
65                  70                  75                  80  


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Ser Gly Lys Gln Phe 
                85                  90                  95      


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


Ile Ser Lys Thr Pro Gly Gln Ala His Gln Pro Asn Val Tyr Val Leu 
        115                 120                 125             


Pro Pro Ser Arg Asp Glu Met Ser Lys Asn Thr Val Thr Leu Thr Cys 
    130                 135                 140                 


Leu Val Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser 
145                 150                 155                 160 


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


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
            180                 185                 190         


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
        195                 200                 205             


Glu Ala Leu His Asn His Tyr Thr Gln Ile Ser Leu Ser His Ser Pro 
    210                 215                 220                 


Gly 
225 


<210>  17
<211>  225
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment dIgGD

<400>  17

Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val 
1               5                   10                  15      


Phe Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr 
            20                  25                  30          


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


Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys 
    50                  55                  60                  


Thr Gln Pro Arg Glu Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys 
                85                  90                  95      


Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile 
            100                 105                 110         


Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro 
        115                 120                 125             


Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys 
    130                 135                 140                 


Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser 
145                 150                 155                 160 


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


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
            180                 185                 190         


Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala Val Met His 
        195                 200                 205             


Glu Ala Leu Gln Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro 
    210                 215                 220                 


Gly 
225 


<210>  18
<211>  224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment dIgGB-cNg-S

<400>  18

Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val 
1               5                   10                  15      


Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr 
            20                  25                  30          


Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu 
        35                  40                  45              


Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys 
    50                  55                  60                  


Thr Gln Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr 
                85                  90                  95      


Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile 
            100                 105                 110         


Ser Lys Ala Arg Gly Gln Ala His Gln Pro Ser Val Tyr Val Leu Pro 
        115                 120                 125             


Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu 
    130                 135                 140                 


Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn 
145                 150                 155                 160 


Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu 
                165                 170                 175     


Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys 
            180                 185                 190         


Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu 
        195                 200                 205             


Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    210                 215                 220                 


<210>  19
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  19

Gly Gly Gly Gly Gln Gly Gly Gly Gly 
1               5                   


<210>  20
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein


<220>
<221>  Xaa
<222>  (10)..(10)
<223>  Xaa is not D

<220>
<221>  Xaa
<222>  (45)..(45)
<223>  Xaa is not H

<220>
<221>  Xaa
<222>  (58)..(58)
<223>  Xaa is absent or N

<400>  20

Phe Val Asn Gln His Leu Cys Gly Ser Xaa Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Xaa Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Xaa Gly Gly Gly Gly Gly Gln 
    50                  55                  60                  


Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp 
65                  70                  75                  80  


Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe 
                85                  90                  95      


Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro 
            100                 105                 110         


Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val 
        115                 120                 125             


Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr 
    130                 135                 140                 


Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val 
145                 150                 155                 160 


Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys 
                165                 170                 175     


Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser 
            180                 185                 190         


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


Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  21
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein


<220>
<221>  Xaa
<222>  (58)..(58)
<223>  Xaa is absent or N

<400>  21

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Xaa Gly Gly Gly Gly Gly Gln 
    50                  55                  60                  


Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp 
65                  70                  75                  80  


Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe 
                85                  90                  95      


Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro 
            100                 105                 110         


Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val 
        115                 120                 125             


Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr 
    130                 135                 140                 


Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val 
145                 150                 155                 160 


Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys 
                165                 170                 175     


Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser 
            180                 185                 190         


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


Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  22
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein


<220>
<221>  Xaa
<222>  (10)..(10)
<223>  Xaa is not D

<220>
<221>  Xaa
<222>  (45)..(45)
<223>  Xaa is not H

<400>  22

Phe Val Asn Gln His Leu Cys Gly Ser Xaa Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Xaa Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  23
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Leader sequence cDNA

<400>  23
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactcc          57


<210>  24
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Leader sequence

<400>  24

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


Val His Ser 
            


<210>  25
<211>  966
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  25
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggaactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agactgcccc      300

aagtgccccg ctcccgagat gctgggcgga cccagcgtgt tcatcttccc tcccaagccc      360

aaggacacac tgctgatcgc caggaccccg gaggtgacct gcgtggtggt ggacctggat      420

cccgaagacc ccgaggtgca gatcagctgg ttcgtggatg gaaagcagat gcagaccgcc      480

aagacccaac cccgggaaga gcagttcaac ggcacctaca gggtggtgag tgtgttgccc      540

atcggccacc aggactggct gaaggggaag caattcacat gcaaggttaa taacaaggcc      600

ctgcccagcc ccatcgagag gaccatcagc aaggccaggg gccaggccca ccagccatct      660

gtgtacgtgc tgcccccatc tagggaggaa ctgagcaaga acacagtcag ccttacttgc      720

ctgatcaagg acttcttccc accggacata gacgtggagt ggcagagtaa cggccagcag      780

gagcccgaga gcaagtatag gaccacaccg ccccaactgg acgaggacgg aagctacttc      840

ctctacagca aattgagcgt tgacaaaagc aggtggcagc gaggcgacac cttcatctgc      900

gccgtgatgc acgaggcttt gcataaccac tacacccagg agagcctgtc ccacagcccc      960

ggatag                                                                 966


<210>  26
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  26

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  27
<211>  969
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  27
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggaactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcaa cggtggcgga      240

ggtggtcaag gaggcggtgg acagggtgga ggtgggcagg gaggaggcgg gggagactgc      300

cccaagtgcc ccgctcccga gatgctgggc ggacccagcg tgttcatctt ccctcccaag      360

cccaaggaca cactgctgat cgccaggacc ccggaggtga cctgcgtggt ggtggacctg      420

gatcccgaag accccgaggt gcagatcagc tggttcgtgg atggaaagca gatgcagacc      480

gccaagaccc aaccccggga agagcagttc aacggcacct acagggtggt gagtgtgttg      540

cccatcggcc accaggactg gctgaagggg aagcaattca catgcaaggt taataacaag      600

gccctgccca gccccatcga gaggaccatc agcaaggcca ggggccaggc ccaccagcca      660

tctgtgtacg tgctgccccc atctagggag gaactgagca agaacacagt cagccttact      720

tgcctgatca aggacttctt cccaccggac atagacgtgg agtggcagag taacggccag      780

caggagcccg agagcaagta taggaccaca ccgccccaac tggacgagga cggaagctac      840

ttcctctaca gcaaattgag cgttgacaaa agcaggtggc agcgaggcga caccttcatc      900

tgcgccgtga tgcacgaggc tttgcataac cactacaccc aggagagcct gtcccacagc      960

cccggatag                                                              969


<210>  28
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  28

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Gly Gln 
    50                  55                  60                  


Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp 
65                  70                  75                  80  


Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe 
                85                  90                  95      


Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro 
            100                 105                 110         


Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val 
        115                 120                 125             


Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr 
    130                 135                 140                 


Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val 
145                 150                 155                 160 


Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys 
                165                 170                 175     


Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser 
            180                 185                 190         


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


Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  29
<211>  966
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  29
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agactgcccc      300

aagtgccccg ctcccgagat gctgggcgga cccagcgtgt tcatcttccc tcccaagccc      360

aaggacacac tgctgatcgc caggaccccg gaggtgacct gcgtggtggt ggacctggat      420

cccgaagacc ccgaggtgca gatcagctgg ttcgtggatg gaaagcagat gcagaccgcc      480

aagacccaac cccgggaaga gcagttctca ggcacctaca gggtggtgag tgtgttgccc      540

atcggccacc aggactggct gaaggggaag caattcacat gcaaggttaa taacaaggcc      600

ctgcccagcc ccatcgagag gaccatcagc aaggccaggg gccaggccca ccagccatct      660

gtgtacgtgc tgcccccatc tagggaggaa ctgagcaaga acacagtcag ccttacttgc      720

ctgatcaagg acttcttccc accggacata gacgtggagt ggcagagtaa cggccagcag      780

gagcccgaga gcaagtatag gaccacaccg ccccaactgg acgaggacgg aagctacttc      840

ctctacagca aattgagcgt tgacaaaagc aggtggcagc gaggcgacac cttcatctgc      900

gccgtgatgc acgaggcttt gcataaccac tacacccagg agagcctgtc ccacagcccc      960

ggatag                                                                 966


<210>  30
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  30

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  31
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  31

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu 
65                  70                  75                  80  


Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu 
                85                  90                  95      


Arg Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly 
            100                 105                 110         


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


Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr 
145                 150                 155                 160 


Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro 
                165                 170                 175     


Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser 
            180                 185                 190         


Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr 
        195                 200                 205             


Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg 
225                 230                 235                 240 


Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr 
            260                 265                 270         


Cys Ala Val Met His Glu Thr Leu Gln Asn His Tyr Thr Asp Leu Ser 
        275                 280                 285             


Leu Ser His Ser Pro Gly 
    290                 


<210>  32
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  32

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu 
65                  70                  75                  80  


Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu 
                85                  90                  95      


Arg Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly 
            100                 105                 110         


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


Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr 
145                 150                 155                 160 


Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro 
                165                 170                 175     


Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser 
            180                 185                 190         


Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr 
        195                 200                 205             


Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg 
225                 230                 235                 240 


Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr 
            260                 265                 270         


Cys Ala Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln Lys Ser 
        275                 280                 285             


Leu Ser Leu Ser Pro Gly 
    290                 


<210>  33
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  33

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu 
65                  70                  75                  80  


Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu 
                85                  90                  95      


Arg Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly 
            100                 105                 110         


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


Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr 
145                 150                 155                 160 


Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro 
                165                 170                 175     


Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser 
            180                 185                 190         


Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr 
        195                 200                 205             


Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg 
225                 230                 235                 240 


Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr 
            260                 265                 270         


Cys Ala Val Leu His Glu Thr Leu Gln Ser His Tyr Thr Asp Leu Ser 
        275                 280                 285             


Leu Ser His Ser Pro Gly 
    290                 


<210>  34
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  34

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu 
65                  70                  75                  80  


Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu 
                85                  90                  95      


Arg Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly 
            100                 105                 110         


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


Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr 
145                 150                 155                 160 


Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro 
                165                 170                 175     


Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser 
            180                 185                 190         


Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr 
        195                 200                 205             


Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg 
225                 230                 235                 240 


Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr 
            260                 265                 270         


Cys Ala Val Met His Glu Thr Leu Gln Ser His Tyr Thr Asp Leu Ser 
        275                 280                 285             


Leu Ser His Ser Pro Gly 
    290                 


<210>  35
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  35

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Arg Cys Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu 
65                  70                  75                  80  


Gly Gly Pro Ser Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu 
                85                  90                  95      


Arg Ile Thr Arg Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly 
            100                 105                 110         


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


Val His Thr Ala Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr 
145                 150                 155                 160 


Gly Lys Glu Phe Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro 
                165                 170                 175     


Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser 
            180                 185                 190         


Val Tyr Val Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr 
        195                 200                 205             


Val Ser Ile Thr Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg 
225                 230                 235                 240 


Met Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr 
            260                 265                 270         


Cys Ala Val Leu His Glu Thr Leu Gln Asn His Tyr Thr Asp Leu Ser 
        275                 280                 285             


Leu Ser His Ser Pro Gly 
    290                 


<210>  36
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  36

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


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


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  37
<211>  291
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  37

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Cys Asn Asn Cys Pro Cys Pro Gly Cys Gly Leu Leu Gly Gly 
65                  70                  75                  80  


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


Ala Arg Thr Pro Thr Val Thr Cys Val Val Val Asp Leu Asp Pro Glu 
            100                 105                 110         


Asn Pro Glu Val Gln Ile Ser Trp Phe Val Asp Ser Lys Gln Val Gln 
        115                 120                 125             


Thr Ala Asn Thr Gln Pro Arg Glu Glu Gln Ser Asn Gly Thr Tyr Arg 
    130                 135                 140                 


Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Ser Gly Lys 
145                 150                 155                 160 


Gln Phe Lys Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu 
                165                 170                 175     


Glu Ile Ile Ser Lys Thr Pro Gly Gln Ala His Gln Pro Asn Val Tyr 
            180                 185                 190         


Val Leu Pro Pro Ser Arg Asp Glu Met Ser Lys Asn Thr Val Thr Leu 
        195                 200                 205             


Thr Cys Leu Val Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp 
    210                 215                 220                 


Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Met Thr Pro 
225                 230                 235                 240 


Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser 
                245                 250                 255     


Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val 
            260                 265                 270         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Ile Ser Leu Ser His 
        275                 280                 285             


Ser Pro Gly 
    290     


<210>  38
<211>  291
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  38

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Cys Ile Ser Pro Cys Pro Val Pro Glu Ser Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Ile Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr 
        115                 120                 125             


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


Val Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly Lys Glu 
145                 150                 155                 160 


Phe Lys Cys Arg Val Asn His Ile Gly Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Thr Leu 
        195                 200                 205             


Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp 
    210                 215                 220                 


Gln Ser Asn Gly Gln Pro Glu Pro Glu Ser Lys Tyr His Thr Thr Ala 
225                 230                 235                 240 


Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser 
                245                 250                 255     


Val Asp Lys Ser Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala Val 
            260                 265                 270         


Met His Glu Ala Leu Gln Asn His Tyr Thr Asp Leu Ser Leu Ser His 
        275                 280                 285             


Ser Pro Gly 
    290     


<210>  39
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  39

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Gln Gly Thr Tyr Arg Val 
    130                 135                 140                 


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  40
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  40

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


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


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  41
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  41

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Asp Gly Thr Tyr Arg Val 
    130                 135                 140                 


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  42
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  42

Phe Val Asn Gln His Leu Cys Gly Ser Asp Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys His Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Lys Gly Thr Tyr Arg Val 
    130                 135                 140                 


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  43
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  43

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Gln Gly Thr Tyr Arg Val 
    130                 135                 140                 


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  44
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  44

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Gln Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  45
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  45

Phe Val Asn Gln His Leu Cys Gly Ser Glu Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  46
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  46

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Ala Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  47
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  47

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Tyr Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  48
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  48

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  49
<211>  292
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  49

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Gln Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gln Arg 
            20                  25                  30          


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


Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala 
    50                  55                  60                  


Gly Gly Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly 
65                  70                  75                  80  


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


Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro 
            100                 105                 110         


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


Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr 
    130                 135                 140                 


Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly 
145                 150                 155                 160 


Lys Gln Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile 
                165                 170                 175     


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


Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser 
        195                 200                 205             


Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu 
    210                 215                 220                 


Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr 
225                 230                 235                 240 


Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu 
                245                 250                 255     


Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala 
            260                 265                 270         


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser 
        275                 280                 285             


His Ser Pro Gly 
    290         


<210>  50
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  50

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys 
        35                  40                  45              


Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly 
    50                  55                  60                  


Gly Ala Gly Gly Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met 
65                  70                  75                  80  


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


Leu Leu Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu 
            100                 105                 110         


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


Gln Met Gln Thr Ala Lys Thr Gln Pro Arg Glu Glu Gln Phe Ser Gly 
    130                 135                 140                 


Thr Tyr Arg Val Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu 
145                 150                 155                 160 


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


Pro Ile Glu Arg Thr Ile Ser Lys Ala Arg Gly Gln Ala His Gln Pro 
            180                 185                 190         


Ser Val Tyr Val Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr 
        195                 200                 205             


Val Ser Leu Thr Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp 
    210                 215                 220                 


Val Glu Trp Gln Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg 
225                 230                 235                 240 


Thr Thr Pro Pro Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser 
                245                 250                 255     


Lys Leu Ser Val Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile 
            260                 265                 270         


Cys Ala Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser 
        275                 280                 285             


Leu Ser His Ser Pro Gly 
    290                 


<210>  51
<211>  290
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  51

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Gly Gly Gly 
            20                  25                  30          


Gly Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys 
        35                  40                  45              


Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro 
65                  70                  75                  80  


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp 
            100                 105                 110         


Pro Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr 
        115                 120                 125             


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


Val Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln 
145                 150                 155                 160 


Phe Thr Cys Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg 
                165                 170                 175     


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


Leu Pro Pro Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr 
        195                 200                 205             


Cys Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln 
    210                 215                 220                 


Ser Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro 
225                 230                 235                 240 


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
                245                 250                 255     


Asp Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met 
            260                 265                 270         


His Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser 
        275                 280                 285             


Pro Gly 
    290 


<210>  52
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  52

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Gly Gly Gly Gly 
            20                  25                  30          


Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  53
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  53

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly Gly 
    50                  55                  60                  


Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys Pro 
65                  70                  75                  80  


Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile Phe 
                85                  90                  95      


Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu Val 
            100                 105                 110         


Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln Ile 
        115                 120                 125             


Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln Pro 
    130                 135                 140                 


Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser Val Leu Pro 
145                 150                 155                 160 


Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys Val 
                165                 170                 175     


Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys Ala 
            180                 185                 190         


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


Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys Asp 
    210                 215                 220                 


Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln Gln 
225                 230                 235                 240 


Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu Asp 
                245                 250                 255     


Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg Trp 
            260                 265                 270         


Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu His 
        275                 280                 285             


Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300     


<210>  54
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  54

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Gln Gly Gly Gly Gly 
            20                  25                  30          


Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly Gly 
    50                  55                  60                  


Gly Asp Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser 
65                  70                  75                  80  


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


Thr Pro Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro 
            100                 105                 110         


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala 
        115                 120                 125             


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


Ser Val Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe 
145                 150                 155                 160 


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


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


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


Leu Ile Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser 
    210                 215                 220                 


Asn Gly Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln 
225                 230                 235                 240 


Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp 
                245                 250                 255     


Lys Ser Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His 
            260                 265                 270         


Glu Ala Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro 
        275                 280                 285             


Gly 
    


<210>  55
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  55

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  56
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  56

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Asn His Gly Gly Gly Gly Gln 
    50                  55                  60                  


Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp 
65                  70                  75                  80  


Cys Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe 
                85                  90                  95      


Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro 
            100                 105                 110         


Glu Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val 
        115                 120                 125             


Gln Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr 
    130                 135                 140                 


Gln Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val 
145                 150                 155                 160 


Leu Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys 
                165                 170                 175     


Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser 
            180                 185                 190         


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


Ser Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  57
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  57

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Asn Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  58
<211>  306
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  58

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Arg Cys 
65                  70                  75                  80  


Thr Asp Thr Pro Pro Cys Pro Val Pro Glu Pro Leu Gly Gly Pro Ser 
                85                  90                  95      


Val Leu Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg 
            100                 105                 110         


Thr Pro Glu Val Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp Pro 
        115                 120                 125             


Glu Val Gln Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr Ala 
    130                 135                 140                 


Lys Thr Gln Ser Arg Glu Gln Gln Phe Asn Gly Thr Tyr Arg Val Val 
145                 150                 155                 160 


Ser Val Leu Pro Ile Glu His Gln Asp Trp Leu Thr Gly Lys Glu Phe 
                165                 170                 175     


Lys Cys Arg Val Asn His Ile Asp Leu Pro Ser Pro Ile Glu Arg Thr 
            180                 185                 190         


Ile Ser Lys Ala Arg Gly Arg Ala His Lys Pro Ser Val Tyr Val Leu 
        195                 200                 205             


Pro Pro Ser Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Ser Ile Thr 
    210                 215                 220                 


Cys Leu Ile Lys Asp Phe Tyr Pro Pro Asp Ile Asp Val Glu Trp Gln 
225                 230                 235                 240 


Ser Asn Gly Gln Gln Glu Pro Glu Arg Lys His Arg Met Thr Pro Pro 
                245                 250                 255     


Gln Leu Asp Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
            260                 265                 270         


Asp Lys Ser Arg Trp Gln Gln Gly Asp Pro Phe Thr Cys Ala Val Met 
        275                 280                 285             


His Glu Thr Leu Gln Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser 
    290                 295                 300                 


Pro Gly 
305     


<210>  59
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  59

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Cys Asn 
65                  70                  75                  80  


Asn Cys Pro Cys Pro Gly Cys Gly Leu Leu Gly Gly Pro Ser Val Phe 
                85                  90                  95      


Ile Phe Pro Pro Lys Pro Lys Asp Ile Leu Val Thr Ala Arg Thr Pro 
            100                 105                 110         


Thr Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asn Pro Glu Val 
        115                 120                 125             


Gln Ile Ser Trp Phe Val Asp Ser Lys Gln Val Gln Thr Ala Asn Thr 
    130                 135                 140                 


Gln Pro Arg Glu Glu Gln Ser Asn Gly Thr Tyr Arg Val Val Ser Val 
145                 150                 155                 160 


Leu Pro Ile Gly His Gln Asp Trp Leu Ser Gly Lys Gln Phe Lys Cys 
                165                 170                 175     


Lys Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Glu Ile Ile Ser 
            180                 185                 190         


Lys Thr Pro Gly Gln Ala His Gln Pro Asn Val Tyr Val Leu Pro Pro 
        195                 200                 205             


Ser Arg Asp Glu Met Ser Lys Asn Thr Val Thr Leu Thr Cys Leu Val 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Gln Glu Pro Glu Ser Lys Tyr Arg Met Thr Pro Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu His Asn His Tyr Thr Gln Ile Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  60
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  60

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Cys Ile 
65                  70                  75                  80  


Ser Pro Cys Pro Val Pro Glu Ser Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Ile Leu Arg Ile Thr Arg Thr Pro Glu 
            100                 105                 110         


Ile Thr Cys Val Val Leu Asp Leu Gly Arg Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Glu Val His Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Gln Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Glu His Gln Asp Trp Leu Thr Gly Lys Glu Phe Lys Cys Arg 
                165                 170                 175     


Val Asn His Ile Gly Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Pro Lys Glu Leu Ser Ser Ser Asp Thr Val Thr Leu Thr Cys Leu Ile 
    210                 215                 220                 


Lys Asp Phe Phe Pro Pro Glu Ile Asp Val Glu Trp Gln Ser Asn Gly 
225                 230                 235                 240 


Gln Pro Glu Pro Glu Ser Lys Tyr His Thr Thr Ala Pro Gln Leu Asp 
                245                 250                 255     


Glu Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser 
            260                 265                 270         


Arg Trp Gln Gln Gly Asp Thr Phe Thr Cys Ala Val Met His Glu Ala 
        275                 280                 285             


Leu Gln Asn His Tyr Thr Asp Leu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300             


<210>  61
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  61

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Ala Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  62
<211>  302
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  62

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Cys 
65                  70                  75                  80  


Pro Lys Cys Pro Ala Pro Glu Met Leu Gly Gly Pro Ser Val Phe Ile 
                85                  90                  95      


Phe Pro Pro Lys Pro Lys Asp Thr Leu Leu Ile Ala Arg Thr Pro Glu 
            100                 105                 110         


Val Thr Cys Val Val Val Asp Leu Asp Pro Glu Asp Pro Glu Val Gln 
        115                 120                 125             


Ile Ser Trp Phe Val Asp Gly Lys Gln Met Gln Thr Ala Lys Thr Gln 
    130                 135                 140                 


Pro Arg Glu Glu Gln Phe Ser Gly Thr Tyr Arg Val Val Ser Val Leu 
145                 150                 155                 160 


Pro Ile Gly His Gln Asp Trp Leu Lys Gly Lys Gln Phe Thr Cys Lys 
                165                 170                 175     


Val Asn Asn Lys Ala Leu Pro Ser Pro Ile Glu Arg Thr Ile Ser Lys 
            180                 185                 190         


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


Arg Glu Glu Leu Ser Lys Asn Thr Val Ser Leu Thr Cys Leu Ile Lys 
    210                 215                 220                 


Asp Phe Phe Pro Pro Asp Ile Asp Val Glu Trp Gln Ser Asn Gly Gln 
225                 230                 235                 240 


Gln Glu Pro Glu Ser Lys Tyr Arg Thr Thr Pro Pro Gln Leu Asp Glu 
                245                 250                 255     


Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val Asp Lys Ser Arg 
            260                 265                 270         


Trp Gln Arg Gly Asp Thr Phe Ile Cys Ala Val Met His Glu Ala Leu 
        275                 280                 285             


His Asn His Tyr Thr Gln Glu Ser Leu Ser His Ser Pro Gly 
    290                 295                 300         


<210>  63
<211>  57
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin Polypeptide

<400>  63

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Pro Thr Gly Gly 
            20                  25                  30          


Gly Pro Arg Arg Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser 
        35                  40                  45              


Leu Tyr Gln Leu Glu Asn Tyr Cys Asn 
    50                  55          


<210>  64
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  64

Gly Gly Gly Gly Gly Ala Gly Gly Gly Gly 
1               5                   10  


<210>  65
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  65

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


Gly Gly Gly 
            


<210>  66
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  66

Gly Gly Gly Gly Lys Gly Gly Gly Gly Lys Gly Gly Gly Gly Lys Gly 
1               5                   10                  15      


Gly Gly Gly 
            


<210>  67
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  67

Gly Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala 
1               5                   10                  15      


Gly Gly Gly Gly Gly 
            20      


<210>  68
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  68

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


Gly Gly Gly Gly Gly 
            20      


<210>  69
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  69

His Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln 
1               5                   10                  15      


Gly Gly Gly Gly Gly 
            20      


<210>  70
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  70

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


Gln Gly Gly Gly Gly Gly 
            20          


<210>  71
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-Chain

<400>  71

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


<210>  72
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-Chain

<400>  72

Gly Gly Ser Gly Gly Gly Gly 
1               5           


<210>  73
<211>  226
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment hIgG1

<400>  73

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly 
225     


<210>  74
<211>  221
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment hIgG2

<400>  74

Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
1               5                   10                  15      


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            20                  25                  30          


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        35                  40                  45              


Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    50                  55                  60                  


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


Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                85                  90                  95      


Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            100                 105                 110         


Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        115                 120                 125             


Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    130                 135                 140                 


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


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp 
                165                 170                 175     


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        195                 200                 205             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    210                 215                 220     


<210>  75
<211>  299
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  75

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Glu Cys 
65                  70                  75                  80  


Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe 
                85                  90                  95      


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
            100                 105                 110         


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe 
        115                 120                 125             


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
    130                 135                 140                 


Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr 
145                 150                 155                 160 


Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
                165                 170                 175     


Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 
            180                 185                 190         


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
        195                 200                 205             


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
    210                 215                 220                 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
225                 230                 235                 240 


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser 
                245                 250                 255     


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
            260                 265                 270         


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
        275                 280                 285             


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 


<210>  76
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  76

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  77
<211>  226
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc Fragment hIgG1 Consensus


<220>
<221>  Xaa
<222>  (77)..(77)
<223>  Xaa is S,D,A,R or Q

<400>  77

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly 
225     


<210>  78
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  78

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ser Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  79
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  79
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca gcagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


<210>  80
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  80

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asp Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  81
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  81
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtacg acagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


<210>  82
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  82

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  83
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  83
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtacg ccagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


<210>  84
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  84

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Arg Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  85
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  85
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca gaagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


<210>  86
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  86

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gln Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  87
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  87

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Ala Gly 
    50                  55                  60                  


Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ser Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  88
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  88
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtgcaggag gcggtggagc cggtggaggt ggggctggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca gcagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


<210>  89
<211>  292
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  89

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Ala Gly Gly 
    50                  55                  60                  


Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
65                  70                  75                  80  


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                85                  90                  95      


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            100                 105                 110         


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        115                 120                 125             


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


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
145                 150                 155                 160 


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                165                 170                 175     


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


Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
        195                 200                 205             


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    210                 215                 220                 


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


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
                245                 250                 255     


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            260                 265                 270         


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        275                 280                 285             


Leu Ser Pro Gly 
    290         


<210>  90
<211>  936
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  90
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

gccggaggcg ggggagacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg      300

gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg      360

acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc      420

aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag      480

tacagcagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat      540

ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc      600

atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatcccgg      660

gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc      720

gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct      780

cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc      840

aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac      900

tacacgcaga agagcctctc cctgtctccg ggttag                                936


<210>  91
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  91

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ser Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  92
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  92

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asp Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  93
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  93

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  94
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  94

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Arg Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  95
<211>  304
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  95

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Glu 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Asp Lys 
65                  70                  75                  80  


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
                85                  90                  95      


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
            100                 105                 110         


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
        115                 120                 125             


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
    130                 135                 140                 


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gln Ser Thr Tyr Arg Val 
145                 150                 155                 160 


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


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


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
        195                 200                 205             


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
    210                 215                 220                 


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
225                 230                 235                 240 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
                245                 250                 255     


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
            260                 265                 270         


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
        275                 280                 285             


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 300                 


<210>  96
<211>  309
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  96

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gly Gln Gly 
    50                  55                  60                  


Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gly Gln Gly 
65                  70                  75                  80  


Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
                85                  90                  95      


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
            100                 105                 110         


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
        115                 120                 125             


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
    130                 135                 140                 


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ser 
145                 150                 155                 160 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
                165                 170                 175     


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
            180                 185                 190         


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
        195                 200                 205             


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
    210                 215                 220                 


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
225                 230                 235                 240 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
                245                 250                 255     


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
            260                 265                 270         


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
        275                 280                 285             


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
    290                 295                 300                 


Ser Leu Ser Pro Gly 
305                 


<210>  97
<211>  292
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  97

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Gly Gly Gly Gly Gln Gly Gly 
    50                  55                  60                  


Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
65                  70                  75                  80  


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                85                  90                  95      


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            100                 105                 110         


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        115                 120                 125             


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


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
145                 150                 155                 160 


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                165                 170                 175     


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


Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
        195                 200                 205             


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    210                 215                 220                 


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


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
                245                 250                 255     


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            260                 265                 270         


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        275                 280                 285             


Leu Ser Pro Gly 
    290         


<210>  98
<211>  283
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin-Fc Fusion Protein

<400>  98

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Ala 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe His Tyr Gly Gly Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Gly Ile Val Glu Gln Cys Cys Thr Ser Thr Cys 
        35                  40                  45              


Ser Leu Asp Gln Leu Glu Asn Tyr Cys Asp Lys Thr His Thr Cys Pro 
    50                  55                  60                  


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


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


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
            100                 105                 110         


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


Arg Glu Glu Gln Tyr Ser Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
    130                 135                 140                 


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


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
                165                 170                 175     


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


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


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


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


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


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


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        275                 280             


<210>  99
<211>  26
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  99

Gly Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln 
1               5                   10                  15      


Gly Gly Gly Gly Gly Gln Gly Gly Gly Gly 
            20                  25      


<210>  100
<211>  972
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA for Insulin-Fc Fusion Protein

<400>  100
atggaatgga gctgggtctt tctcttcttc ctgtcagtaa cgactggtgt ccactccttc       60

gtgaaccagc acctgtgcgg ctcccacctg gtggaagctc tggcactcgt gtgcggcgag      120

cggggcttcc actacggggg tggcggagga ggttctggtg gcggcggagg catcgtggaa      180

cagtgctgca cctccacctg ctccctggac cagctggaaa actactgcgg tggcggaggt      240

ggtcaaggag gcggtggaca gggtggaggt gggcagggag gaggcggggg agacaaaact      300

cacacatgcc caccgtgccc agcacctgaa ctcctggggg gaccgtcagt cttcctcttc      360

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg      420

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag      480

gtgcataatg ccaagacaaa gccgcgggag gagcagtacc aaagcacgta ccgtgtggtc      540

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc      600

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc      660

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc      720

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc      780

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc      840

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc      900

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg      960

tctccgggtt ag                                                          972


