                         SEQUENCE LISTING

<110>  OPKO Biologics Ltd.
 
<120>  LONG-ACTING IGF-1 OR IGF-1 VARIANTS AND METHODS OF PRODUCING SAME

<130>  P-585046-PC

<150>  62/872,925
<151>  2019-07-11

<160>  28    

<170>  PatentIn version 3.5

<210>  1
<211>  70
<212>  PRT
<213>  Homo sapiens

<400>  1

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


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


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


Lys Pro Ala Lys Ser Ala 
65                  70  


<210>  2
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys 
            20      


<210>  3
<211>  27
<212>  PRT
<213>  Homo sapiens

<400>  3

Val Lys Met His Thr Met Ser Ser Ser His Leu Phe Tyr Leu Ala Leu 
1               5                   10                  15      


Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
            20                  25          


<210>  4
<211>  77
<212>  PRT
<213>  Homo sapiens

<400>  4

Arg Ser Val Arg Ala Gln Arg His Thr Asp Met Pro Lys Thr Gln Lys 
1               5                   10                  15      


Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr Lys Ser Gln Arg Arg Lys 
            20                  25                  30          


Gly Trp Pro Lys Thr His Pro Gly Gly Glu Gln Lys Glu Gly Thr Glu 
        35                  40                  45              


Ala Ser Leu Gln Ile Arg Gly Lys Lys Lys Glu Gln Arg Arg Glu Ile 
    50                  55                  60                  


Gly Ser Arg Asn Ala Glu Cys Arg Gly Lys Lys Gly Lys 
65                  70                  75          


<210>  5
<211>  195
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu 
            20                  25                  30          


Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
        35                  40                  45              


Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
    50                  55                  60                  


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
65                  70                  75                  80  


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
            100                 105                 110         


Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp 
        115                 120                 125             


Met Pro Lys Thr Gln Lys Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr 
    130                 135                 140                 


Lys Ser Gln Arg Arg Lys Gly Trp Pro Lys Thr His Pro Gly Gly Glu 
145                 150                 155                 160 


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


Glu Gln Arg Arg Glu Ile Gly Ser Arg Asn Ala Glu Cys Arg Gly Lys 
            180                 185                 190         


Lys Gly Lys 
        195 


<210>  6
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP sequence

<400>  6

Asp Pro Arg Phe Gln Asp Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
1               5                   10                  15      


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
            20                  25                  30          


Gln 
    


<210>  7
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP sequence

<400>  7

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
            20                  25              


<210>  8
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Truncated CTP sequence

<400>  8

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro 
1               5                   10          


<210>  9
<211>  26
<212>  PRT
<213>  Homo sapiens

<400>  9

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala 
            20                  25      


<210>  10
<211>  180
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-1

<400>  10

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala Ser Ser Ser Ser Lys Ala 
            20                  25                  30          


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
        35                  40                  45              


Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
    50                  55                  60                  


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
65                  70                  75                  80  


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
                85                  90                  95      


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Gly Pro 
            100                 105                 110         


Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe Val Cys 
        115                 120                 125             


Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser 
    130                 135                 140                 


Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys Phe Arg 
145                 150                 155                 160 


Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro 
                165                 170                 175     


Ala Lys Ser Ala 
            180 


<210>  11
<211>  230
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-2

<400>  11

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu 
            20                  25                  30          


Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
        35                  40                  45              


Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
    50                  55                  60                  


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
65                  70                  75                  80  


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
            100                 105                 110         


Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
        115                 120                 125             


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
    130                 135                 140                 


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
145                 150                 155                 160 


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
                165                 170                 175     


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
            180                 185                 190         


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala 
        195                 200                 205             


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
    210                 215                 220                 


Thr Pro Ile Leu Pro Gln 
225                 230 


<210>  12
<211>  202
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-3

<400>  12

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu 
            20                  25                  30          


Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
        35                  40                  45              


Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
    50                  55                  60                  


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
65                  70                  75                  80  


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
            100                 105                 110         


Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
        115                 120                 125             


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
    130                 135                 140                 


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
145                 150                 155                 160 


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
                165                 170                 175     


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
            180                 185                 190         


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
        195                 200         


<210>  13
<211>  180
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-4

<400>  13

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala Ser Ser Ser Ser Lys Ala 
            20                  25                  30          


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
        35                  40                  45              


Thr Pro Ile Leu Pro Gln Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu 
    50                  55                  60                  


Val Asp Ala Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn 
65                  70                  75                  80  


Lys Pro Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly 
                85                  90                  95      


Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu 
            100                 105                 110         


Met Tyr Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser 
        115                 120                 125             


Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
    130                 135                 140                 


Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro 
145                 150                 155                 160 


Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro 
                165                 170                 175     


Ile Leu Pro Gln 
            180 


<210>  14
<211>  264
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-5

<400>  14

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala Ser Ser Ser Ser Lys Ala 
            20                  25                  30          


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
        35                  40                  45              


Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
    50                  55                  60                  


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
65                  70                  75                  80  


Pro Gln Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu 
                85                  90                  95      


Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly 
            100                 105                 110         


Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu 
        115                 120                 125             


Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala 
    130                 135                 140                 


Pro Leu Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro 
145                 150                 155                 160 


Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro 
                165                 170                 175     


Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro 
            180                 185                 190         


Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
        195                 200                 205             


Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
    210                 215                 220                 


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser 
225                 230                 235                 240 


Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
                245                 250                 255     


Ser Asp Thr Pro Ile Leu Pro Gln 
            260                 


<210>  15
<211>  154
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature CTP-modified IGF-1, MOD-1301-1 without the signal peptide

<400>  15

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser 
            20                  25                  30          


Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
        35                  40                  45              


Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro 
    50                  55                  60                  


Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro 
65                  70                  75                  80  


Ile Leu Pro Gln Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp 
                85                  90                  95      


Ala Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro 
            100                 105                 110         


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


Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr 
    130                 135                 140                 


Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala 
145                 150                 


<210>  16
<211>  182
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature CTP-modified IGF-1, MOD-1301-2 without the signal peptide 
       or propeptide

<400>  16

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


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


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
65                  70                  75                  80  


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
                85                  90                  95      


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
            100                 105                 110         


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
        115                 120                 125             


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
    130                 135                 140                 


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala 
145                 150                 155                 160 


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
                165                 170                 175     


Thr Pro Ile Leu Pro Gln 
            180         


<210>  17
<211>  154
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature CTP-modified IGF-1, MOD-1301-3 without the signal peptide 
       or propeptide

<400>  17

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


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


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


Lys Pro Ala Lys Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
65                  70                  75                  80  


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
                85                  90                  95      


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
            100                 105                 110         


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
        115                 120                 125             


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
    130                 135                 140                 


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
145                 150                 


<210>  18
<211>  154
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature CTP-modified IGF-1, MOD-1301-4 without the signal peptide

<400>  18

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Gly Pro Glu Thr 
            20                  25                  30          


Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe Val Cys Gly Asp 
        35                  40                  45              


Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser Ser Arg 
    50                  55                  60                  


Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys Phe Arg Ser Cys 
65                  70                  75                  80  


Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro Ala Lys 
                85                  90                  95      


Ser Ala Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
            100                 105                 110         


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
        115                 120                 125             


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
    130                 135                 140                 


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
145                 150                 


<210>  19
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature CTP-modified IGF-1, MOD-1301-5 without the signal peptide

<400>  19

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser 
            20                  25                  30          


Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
        35                  40                  45              


Ser Asp Thr Pro Ile Leu Pro Gln Gly Pro Glu Thr Leu Cys Gly Ala 
    50                  55                  60                  


Glu Leu Val Asp Ala Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr 
65                  70                  75                  80  


Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln 
                85                  90                  95      


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


Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala Ser Ser 
        115                 120                 125             


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
    130                 135                 140                 


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala 
145                 150                 155                 160 


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
                165                 170                 175     


Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
            180                 185                 190         


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
        195                 200                 205             


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
    210                 215                 220                 


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
225                 230                 235             


<210>  20
<211>  562
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-1

<400>  20
gcggccgcca tggccaccgg gagccggaca tctctgctgc tggctttcgg tctgctgtgc       60

ctgccatggc tgcaggaggg cagtgcttcc agctctagta aggcaccccc tccatcactg      120

ccttcccctt ctagactgcc tggaccatct gacaccccaa tcctgcctca gtcatccagc      180

tctaaagctc cccctccatc tctgccttct ccaagtcgtc tgcccgggcc tagtgataca      240

ccaattctgc cccagagttc atccagcaag gcaccccctc caagcctgcc atcaccatcc      300

aggctgccag gcccatctga cactcctatc ctgccacagg gacctgagac cctgtgcgga      360

gcagaactgg tggacgccct gcagttcgtc tgtggggata gaggtttcta ctttaacaaa      420

cccacaggct atggatctag ttcaaggcgg gcacctcaga ctggcattgt ggacgagtgc      480

tgttttaggt cctgcgatct gagacgcctg gaaatgtact gtgcccctct gaagccagcc      540

aaatccgcct gataagcttt ga                                               562


<210>  21
<211>  712
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  the CTP-modified IGF-1, MOD-1301-2

<400>  21
gcggccgcca tgggcaagat ctccagcctg cctacccagc tgttcaaatg ctgtttctgc       60

gactttctga aggtgaaaat gcacacaatg tctagttcac acctgttcta cctggccctg      120

tgcctgctga cctttacatc cagcgccact gctggaccag agaccctgtg cggagctgaa      180

ctggtggacg cactgcagtt cgtctgtggg gataggggtt tctactttaa caagccaaca      240

ggctatggat ctagttcaag gcgggcccct cagactggga ttgtcgacga gtgctgtttt      300

cggagctgcg atctgagacg cctggaaatg tattgtgccc ctctgaagcc agcaaaatca      360

gcctccagct ctagtaaggc tccccctcca agtctgccta gcccttctag actgcctgga      420

ccatctgaca ctccaatcct gcctcagtca tccagctcta aagcaccccc tccaagcctg      480

cctagtccat cacgtctgcc cggtccttct gataccccaa ttctgcccca gagttcatcc      540

agcaaggccc ctcccccatc cctgccttct cctagcaggc tgccaggccc atctgacaca      600

cctatcctgc cacagtctag ttcatccaaa gctccccctc catctctgcc ctctcctagt      660

agactgccag gaccctccga tacccccatt ctgcctcagt gataagcttt ga              712


<210>  22
<211>  628
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-3

<400>  22
gcggccgcca tgggcaagat ctcttcactg cccacccagt tgttcaagtg ctgtttctgc       60

gactttctga aggtgaagat gcacaccatg agtagctcac acctgtttta tctggccctc      120

tgtctgctca ccttcacttc tagtgccact gccggaccag aaaccctctg cggcgccgaa      180

ctggtggacg cattgcagtt cgtgtgcgga gacaggggtt tctactttaa caagccaaca      240

ggttacggct cctctagcag acgggctccc cagaccggca tcgttgatga gtgctgtttt      300

aggtcctgtg acctcaggcg tctggagatg tattgcgctc ccctgaaacc agccaagtct      360

gcaagctcat cttccaaggc acctccacct tctctgccaa gcccctctag gttgccaggc      420

ccttccgata cccccatttt gcctcagtca tccagcagta aggcaccacc cccttccctg      480

cctagccctt caaggctgcc aggccctagc gataccccaa ttctgccaca gagctcaagc      540

tccaaagccc cacctccctc actgccatcc ccttctcggc tgccaggccc atccgatacc      600

cctatcttgc cacagtgata agctttga                                         628


<210>  23
<211>  562
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-4

<400>  23
gcggccgcca tggctaccgg tagtaggact agcctgctct tggcatttgg tctgctctgt       60

ctgccttggt tgcaggaggg cagtgcctcc agctcctcta aagctcctcc accctctttg      120

ccaagcccct ctagattgcc tggtccatcc gatactccaa ttctgcctca gggccctgag      180

actttgtgcg gcgctgaact ggtggacgca ctccagttcg tctgcggaga cagaggcttc      240

tacttcaaca aacctactgg gtatggttct tccagtcgta gggcaccaca gacaggtatc      300

gtggatgagt gttgcttcag gtcatgtgac ctcaggcgtc tggagatgta ctgtgcacca      360

ctgaagcctg caaaatccgc ctcaagctcc agtaaggctc cacctccttc attgccaagc      420

ccttctcgtc tgcccggtcc aagcgacacc ccaattctgc cccagtcatc ttccagcaaa      480

gccccacctc caagtctgcc cagcccaagt cgactgcctg gaccctctga tacccccatc      540

ctgccacagt gataagcttt ga                                               562


<210>  24
<211>  814
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTP-modified IGF-1, MOD-1301-5

<400>  24
gcggccgcca tggcaacagg tagtaggact tctttgctgc tcgcctttgg actgctgtgc       60

ctcccttggc tgcaggaggg ctcagctagc agcagttcca aggctcctcc cccatctctg      120

ccttcaccca gcaggttgcc cgggccatca gatactccaa tcctccccca gtcttccagt      180

agcaaagccc cacctccctc cctgccttca ccatccaggt tgcctggtcc aagcgataca      240

cctatcctgc cacagggacc tgagacactc tgtggtgcag agctggtgga tgcattgcag      300

tttgtttgcg gcgacagagg gttctacttc aacaagccta ctggctatgg ttctagctcc      360

agaagagcac cacagaccgg aatcgtggat gaatgctgct tccgttcctg cgacttgcgc      420

agactggaga tgtattgtgc cccactcaaa cctgctaagt ccgccagttc tagctccaaa      480

gctcctccac cctcactgcc cagcccatca aggctcccag gaccctcaga tacccccatt      540

ttgcctcagt ctagctccag caaggcacct ccaccctctt tgccctctcc aagcagattg      600

ccaggtccta gtgacactcc catcctgcct cagtcaagct ccagtaaagc ccctccacct      660

agcctcccat ctcccagcag actgccaggt cctagcgata cacccatctt gccccagtca      720

agtagctcca aagctccacc ccctagcctc ccttcaccct ctaggttgcc tggcccatca      780

gatacaccaa ttctcccaca gtgataagct ttga                                  814


<210>  25
<211>  48
<212>  PRT
<213>  Homo sapiens

<400>  25

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu 
            20                  25                  30          


Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
        35                  40                  45              


<210>  26
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-HGH-CTP-CTP Polypeptide without a Signal Sequence

<400>  26

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Phe Pro Thr Ile 
            20                  25                  30          


Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg Ala His Arg Leu 
        35                  40                  45              


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


Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro Gln Thr Ser Leu 
65                  70                  75                  80  


Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg Glu Glu Thr Gln 
                85                  90                  95      


Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu Leu Leu Ile Gln 
            100                 105                 110         


Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val Phe Ala Asn Ser 
        115                 120                 125             


Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp Leu Leu Lys Asp 
    130                 135                 140                 


Leu Glu Glu Gly Ile Gln Thr Leu Met Gly Arg Leu Glu Asp Gly Ser 
145                 150                 155                 160 


Pro Arg Thr Gly Gln Ile Phe Lys Gln Thr Tyr Ser Lys Phe Asp Thr 
                165                 170                 175     


Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr 
            180                 185                 190         


Cys Phe Arg Lys Asp Met Asp Lys Val Glu Thr Phe Leu Arg Ile Val 
        195                 200                 205             


Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe Ser Ser Ser Ser Lys 
    210                 215                 220                 


Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser 
225                 230                 235                 240 


Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro 
                245                 250                 255     


Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile 
            260                 265                 270         


Leu Pro Gln 
        275 


<210>  27
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-HGH-CTP-CTP Polypeptide with the Signal Sequence

<400>  27

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala Ser Ser Ser Ser Lys Ala 
            20                  25                  30          


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
        35                  40                  45              


Thr Pro Ile Leu Pro Gln Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe 
    50                  55                  60                  


Asp Asn Ala Met Leu Arg Ala His Arg Leu His Gln Leu Ala Phe Asp 
65                  70                  75                  80  


Thr Tyr Gln Glu Phe Glu Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr 
                85                  90                  95      


Ser Phe Leu Gln Asn Pro Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile 
            100                 105                 110         


Pro Thr Pro Ser Asn Arg Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu 
        115                 120                 125             


Leu Leu Arg Ile Ser Leu Leu Leu Ile Gln Ser Trp Leu Glu Pro Val 
    130                 135                 140                 


Gln Phe Leu Arg Ser Val Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser 
145                 150                 155                 160 


Asp Ser Asn Val Tyr Asp Leu Leu Lys Asp Leu Glu Glu Gly Ile Gln 
                165                 170                 175     


Thr Leu Met Gly Arg Leu Glu Asp Gly Ser Pro Arg Thr Gly Gln Ile 
            180                 185                 190         


Phe Lys Gln Thr Tyr Ser Lys Phe Asp Thr Asn Ser His Asn Asp Asp 
        195                 200                 205             


Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr Cys Phe Arg Lys Asp Met 
    210                 215                 220                 


Asp Lys Val Glu Thr Phe Leu Arg Ile Val Gln Cys Arg Ser Val Glu 
225                 230                 235                 240 


Gly Ser Cys Gly Phe Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu 
                245                 250                 255     


Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro 
            260                 265                 270         


Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser 
        275                 280                 285             


Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
    290                 295                 300     


<210>  28
<211>  903
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Encoding a CTP-modified hGH polypeptide

<400>  28
atggccaccg gcagcaggac cagcctgctg ctggccttcg gcctgctgtg cctgccatgg       60

ctgcaggagg gcagcgccag ctcttcttct aaggctccac ccccatctct gcccagcccc      120

agcagactgc cgggccccag cgacacaccc attctgcccc agttccccac catccccctg      180

agcaggctgt tcgacaacgc catgctgagg gctcacaggc tgcaccagct ggcctttgac      240

acctaccagg agttcgagga agcctacatc cccaaggagc agaagtacag cttcctgcag      300

aacccccaga cctccctgtg cttcagcgag agcatcccca cccccagcaa cagagaggag      360

acccagcaga agagcaacct ggagctgctg aggatctccc tgctgctgat ccagagctgg      420

ctggagcccg tgcagttcct gagaagcgtg ttcgccaaca gcctggtgta cggcgccagc      480

gacagcaacg tgtacgacct gctgaaggac ctggaggagg gcatccagac cctgatgggc      540

cggctggagg acggcagccc caggaccggc cagatcttca agcagaccta cagcaagttc      600

gacaccaaca gccacaacga cgacgccctg ctgaagaact acgggctgct gtactgcttc      660

agaaaggaca tggacaaggt ggagaccttc ctgaggatcg tgcagtgcag aagcgtggag      720

ggcagctgcg gcttcagctc cagcagcaag gcccctcccc cgagcctgcc ctccccaagc      780

aggctgcctg ggccctccga cacaccaatc ctgccacaga gcagctcctc taaggcccct      840

cctccatccc tgccatcccc ctcccggctg cctggcccct ctgacacccc tatcctgcct      900

cag                                                                    903


