                         SEQUENCE LISTING

<110>  OPKO Biologics Ltd.
       HERSHKOVITZ, Oren
       BAR-ILAN, Ahuva
       MOSCHCOVICH, Laura
       ISRAELI YAGEV, Lital
 
<120>  LONG-ACTING HGH ANTAGONISTS AND METHODS OF PRODUCING SAME

<130>  P-578862-PC

<150>  62/664,911
<151>  2018-04-30

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  32
<212>  PRT
<213>  Homo sapiens

<400>  1

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          


<210>  2
<211>  28
<212>  PRT
<213>  Homo sapiens

<400>  2

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>  3
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  3

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


<210>  4
<211>  191
<212>  PRT
<213>  Homo sapiens

<400>  4

Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg 
1               5                   10                  15      


Ala His Arg Leu His Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 
            20                  25                  30          


Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro 
        35                  40                  45              


Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg 
    50                  55                  60                  


Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 
65                  70                  75                  80  


Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 
                85                  90                  95      


Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 
            100                 105                 110         


Leu Leu Lys Asp Leu Glu Glu Gly Ile Gln Thr Leu Met Gly Arg Leu 
        115                 120                 125             


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


Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 
145                 150                 155                 160 


Gly Leu Leu Tyr Cys Phe Arg Lys Asp Met Asp Lys Val Glu Thr Phe 
                165                 170                 175     


Leu Arg Ile Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 
            180                 185                 190     


<210>  5
<211>  247
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       (MOD1201-1)

<400>  5

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 Asp Arg Leu 
        35                  40                  45              


Asn 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 Lys 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 Asn Lys Asp Met Ser Lys Val Ser Thr Phe Leu Arg Thr 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 
                245         


<210>  6
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       (MOD1201-2)

<400>  6

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 Asp Arg Leu 
        35                  40                  45              


Asn 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 Lys 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 Asn Lys Asp Met Ser Lys Val Ser Thr Phe Leu Arg Thr 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 Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser 
        275                 280                 285             


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


<210>  7
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       (MOD1201-3)

<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 Phe Pro Thr Ile 
            20                  25                  30          


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


Asn 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 Lys 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 Asn Lys Asp Met Ser Lys Val Ser Thr Phe Leu Arg Thr 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>  8
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       (MOD1201-4 )

<400>  8

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 Asp Arg Leu 
        35                  40                  45              


Asn 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 Pro Ser Glu Ser Ile Pro Thr Pro Ser Asn Lys 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 Lys 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 Asn Lys Asp Met Ser Lys Val Ser Thr Phe Leu Arg Thr 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>  9
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       (MOD1201-5)

<400>  9

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 Ala Asp Asn Ala Trp Leu Arg Ala Asp Arg Leu 
        35                  40                  45              


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


Pro Lys Glu Gln Ile His Ser Phe Trp Trp Asn Pro Gln Thr Ser Leu 
65                  70                  75                  80  


Cys Pro Ser Glu Ser Ile Pro Thr Pro Ser Asn Lys 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 Lys 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 Asn Lys Asp Met Ser Lys Val Ser Thr Tyr Leu Arg Thr 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>  10
<211>  26
<212>  PRT
<213>  Homo sapiens

<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 
            20                  25      


<210>  11
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-modified human growth hormone (hGH) antagonist Variant 
       MOD1201-4, including the signal peptide

<400>  11

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 Asp Arg Leu Asn 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 Pro Ser Glu Ser Ile 
            100                 105                 110         


Pro Thr Pro Ser Asn Lys 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 Lys 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 Asn Lys Asp Met 
    210                 215                 220                 


Ser Lys Val Ser Thr Phe Leu Arg Thr 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>  12
<211>  922
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleic acid sequence encoding CTP-modified hGH antagonist 
       Variant MOD1201-4

<400>  12
gcggccgcca tggcaactgg atcacgtaca agcctgttgc tcgctttcgg attgctctgc       60

ctgccttggc tgcaggaagg atctgcaagc tccagttcaa aggctcctcc accatcactg      120

ccttcccctt cacgtttgcc tggaccttcc gataccccta ttctgccaca gttccctact      180

atccctctga gtaggttgtt cgacaacgcc atgttgcggg ctgacagact gaatcagctc      240

gcttttgata cctatcagga gttcgaagag gcctacatcc ccaaagagca gaagtacagt      300

tttctgcaga atcctcagac cagtttgtgc cctagcgaat caatccccac tccatccaac      360

aaggaagaga ctcagcagaa gtctaacctg gaactcctgc ggattagcct gttgctgatc      420

cagagctggt tggaacctgt gcagtttttg aggagtgttt tcgcaaactc cctggtctat      480

ggcgcctctg atagcaatgt ctacgacttg ctgaaggacc tggaggaaaa gatccagact      540

ctgatgggac gactcgagga tggaagtccc aggaccggtc agatctttaa gcagacctac      600

agtaagtttg ataccaactc ccacaatgat gacgccctgc tgaagaacta cggcctcctc      660

tactgtttca acaaggacat gtccaaggtg tctacattcc tgcgcactgt tcagtgtagg      720

agtgtggaag gctcttgcgg attttcttcc agtagcaagg ctccaccccc ttccttgccc      780

agtccatcca ggctgcccgg cccttcagat acccctatcc tgccacagag cagttcatcc      840

aaggctccac ctccctctct gcctagccct tcacgattgc caggcccctc cgacacccct      900

attctcccac agtgataagc tt                                               922


<210>  13
<211>  191
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hGHA variant with at least 6 AA substitutions

<400>  13

Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg 
1               5                   10                  15      


Ala Asp Arg Leu Asn Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 
            20                  25                  30          


Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro 
        35                  40                  45              


Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg 
    50                  55                  60                  


Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 
65                  70                  75                  80  


Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 
                85                  90                  95      


Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 
            100                 105                 110         


Leu Leu Lys Asp Leu Glu Glu Lys Ile Gln Thr Leu Met Gly Arg Leu 
        115                 120                 125             


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


Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 
145                 150                 155                 160 


Gly Leu Leu Tyr Cys Phe Asn Lys Asp Met Ser Lys Val Ser Thr Phe 
                165                 170                 175     


Leu Arg Thr Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 
            180                 185                 190     


<210>  14
<211>  191
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hGHA variant with at least 8 AA substitutions

<400>  14

Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg 
1               5                   10                  15      


Ala Asp Arg Leu Asn Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 
            20                  25                  30          


Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro 
        35                  40                  45              


Gln Thr Ser Leu Cys Pro Ser Glu Ser Ile Pro Thr Pro Ser Asn Lys 
    50                  55                  60                  


Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 
65                  70                  75                  80  


Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 
                85                  90                  95      


Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 
            100                 105                 110         


Leu Leu Lys Asp Leu Glu Glu Lys Ile Gln Thr Leu Met Gly Arg Leu 
        115                 120                 125             


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


Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 
145                 150                 155                 160 


Gly Leu Leu Tyr Cys Phe Asn Lys Asp Met Ser Lys Val Ser Thr Phe 
                165                 170                 175     


Leu Arg Thr Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 
            180                 185                 190     


<210>  15
<211>  191
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hGHA variant with at least 15 AA substitutions

<400>  15

Phe Pro Thr Ile Pro Leu Ser Arg Leu Ala Asp Asn Ala Trp Leu Arg 
1               5                   10                  15      


Ala Asp Arg Leu Asn Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 
            20                  25                  30          


Glu Ala Tyr Ile Pro Lys Glu Gln Ile His Ser Phe Trp Trp Asn Pro 
        35                  40                  45              


Gln Thr Ser Leu Cys Pro Ser Glu Ser Ile Pro Thr Pro Ser Asn Lys 
    50                  55                  60                  


Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 
65                  70                  75                  80  


Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 
                85                  90                  95      


Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 
            100                 105                 110         


Leu Leu Lys Asp Leu Glu Glu Lys Ile Gln Thr Leu Met Gly Arg Leu 
        115                 120                 125             


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


Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 
145                 150                 155                 160 


Gly Leu Leu Tyr Cys Phe Asn Lys Asp Met Ser Lys Val Ser Thr Tyr 
                165                 170                 175     


Leu Arg Thr Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 
            180                 185                 190     


