                         SEQUENCE LISTING

<110>  OPKO BIOLOGICS LTD.
       HERSHKOVITZ, Oren
       MOSCHCOVICH, Laura
 
<120>  LONG-ACTING COAGULATION FACTORS AND METHODS OF PRODUCING SAME

<130>  P-9520-PC9

<150>  62/360,767
<151>  2016-07-11

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  1356
<212>  DNA
<213>  Homo sapiens

<400>  1
ctcgaggaca tggtctccca ggccctcagg ctcctctgcc ttctgcttgg gcttcagggc       60

tgcctggctg cagtcttcgt aacccaggag gaagcccacg gcgtcctgca ccggcgccgg      120

cgcgccaacg cgttcctgga ggagctgcgg ccgggctccc tggagaggga gtgcaaggag      180

gagcagtgct ccttcgagga ggcccgggag atcttcaagg acgcggagag gacgaagctg      240

ttctggattt cttacagtga tggggaccag tgtgcctcaa gtccatgcca gaatgggggc      300

tcctgcaagg accagctcca gtcctatatc tgcttctgcc tccctgcctt cgagggccgg      360

aactgtgaga cgcacaagga tgaccagctg atctgtgtga acgagaacgg cggctgtgag      420

cagtactgca gtgaccacac gggcaccaag cgctcctgtc ggtgccacga ggggtactct      480

ctgctggcag acggggtgtc ctgcacaccc acagttgaat atccatgtgg aaaaatacct      540

attctagaaa aaagaaatgc cagcaaaccc caaggccgaa ttgtgggggg caaggtgtgc      600

cccaaagggg agtgtccatg gcaggtcctg ttgttggtga atggagctca gttgtgtggg      660

gggaccctga tcaacaccat ctgggtggtc tccgcggccc actgtttcga caaaatcaag      720

aactggagga acctgatcgc ggtgctgggc gagcacgacc tcagcgagca cgacggggat      780

gagcagagcc ggcgggtggc gcaggtcatc atccccagca cgtacgtccc gggcaccacc      840

aaccacgaca tcgcgctgct ccgcctgcac cagcccgtgg tcctcactga ccatgtggtg      900

cccctctgcc tgcccgaacg gacgttctct gagaggacgc tggccttcgt gcgcttctca      960

ttggtcagcg gctggggcca gctgctggac cgtggcgcca cggccctgga gctcatggtc     1020

ctcaacgtgc cccggctgat gacccaggac tgcctgcagc agtcacggaa ggtgggagac     1080

tccccaaata tcacggagta catgttctgt gccggctact cggatggcag caaggactcc     1140

tgcaaggggg acagtggagg cccacatgcc acccactacc ggggcacgtg gtacctgacg     1200

ggcatcgtca gctggggcca gggctgcgca accgtgggcc actttggggt gtacaccagg     1260

gtctcccagt acatcgagtg gctgcaaaag ctcatgcgct cagagccacg cccaggagtc     1320

ctcctgcgag ccccatttcc ctgaggatgc ggccgc                               1356


<210>  2
<211>  444
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 
1               5                   10                  15      


Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val 
            20                  25                  30          


Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro 
        35                  40                  45              


Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu 
    50                  55                  60                  


Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile 
65                  70                  75                  80  


Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly 
                85                  90                  95      


Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro 
            100                 105                 110         


Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 
        115                 120                 125             


Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr 
    130                 135                 140                 


Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala 
145                 150                 155                 160 


Asp Gly Val Ser Cys Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile 
                165                 170                 175     


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


Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 
        195                 200                 205             


Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 
    210                 215                 220                 


Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 
225                 230                 235                 240 


Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 
                245                 250                 255     


Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 
            260                 265                 270         


Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 
        275                 280                 285             


Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 
    290                 295                 300                 


Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 
305                 310                 315                 320 


Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 
                325                 330                 335     


Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser 
            340                 345                 350         


Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 
        355                 360                 365             


Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 
    370                 375                 380                 


Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val 
385                 390                 395                 400 


Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 
                405                 410                 415     


Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 
            420                 425                 430         


Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro 
        435                 440                 


<210>  3
<211>  448
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 
1               5                   10                  15      


Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val 
            20                  25                  30          


Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro 
        35                  40                  45              


Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu 
    50                  55                  60                  


Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile 
65                  70                  75                  80  


Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly 
                85                  90                  95      


Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro 
            100                 105                 110         


Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 
        115                 120                 125             


Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr 
    130                 135                 140                 


Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala 
145                 150                 155                 160 


Asp Gly Val Ser Cys Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile 
                165                 170                 175     


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


Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 
        195                 200                 205             


Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 
    210                 215                 220                 


Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 
225                 230                 235                 240 


Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 
                245                 250                 255     


Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 
            260                 265                 270         


Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 
        275                 280                 285             


Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 
    290                 295                 300                 


Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 
305                 310                 315                 320 


Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 
                325                 330                 335     


Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser 
            340                 345                 350         


Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 
        355                 360                 365             


Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 
    370                 375                 380                 


Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val 
385                 390                 395                 400 


Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 
                405                 410                 415     


Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 
            420                 425                 430         


Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro Gly Cys Gly Arg 
        435                 440                 445             


<210>  4
<211>  1621
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTP-Modified Factor VII

<400>  4
ctcgaggaca tggtctccca ggccctcagg ctcctctgcc ttctgcttgg gcttcagggc       60

tgcctggctg cagtcttcgt aacccaggag gaagcccacg gcgtcctgca ccggcgccgg      120

cgcgccaacg cgttcctgga ggagctgcgg ccgggctccc tggagaggga gtgcaaggag      180

gagcagtgct ccttcgagga ggcccgggag atcttcaagg acgcggagag gacgaagctg      240

ttctggattt cttacagtga tggggaccag tgtgcctcaa gtccatgcca gaatgggggc      300

tcctgcaagg accagctcca gtcctatatc tgcttctgcc tccctgcctt cgagggccgg      360

aactgtgaga cgcacaagga tgaccagctg atctgtgtga acgagaacgg cggctgtgag      420

cagtactgca gtgaccacac gggcaccaag cgctcctgtc ggtgccacga ggggtactct      480

ctgctggcag acggggtgtc ctgcacaccc acagttgaat atccatgtgg aaaaatacct      540

attctagaaa aaagaaatgc cagcaaaccc caaggccgaa ttgtgggggg caaggtgtgc      600

cccaaagggg agtgtccatg gcaggtcctg ttgttggtga atggagctca gttgtgtggg      660

gggaccctga tcaacaccat ctgggtggtc tccgcggccc actgtttcga caaaatcaag      720

aactggagga acctgatcgc ggtgctgggc gagcacgacc tcagcgagca cgacggggat      780

gagcagagcc ggcgggtggc gcaggtcatc atccccagca cgtacgtccc gggcaccacc      840

aaccacgaca tcgcgctgct ccgcctgcac cagcccgtgg tcctcactga ccatgtggtg      900

cccctctgcc tgcccgaacg gacgttctct gagaggacgc tggccttcgt gcgcttctca      960

ttggtcagcg gctggggcca gctgctggac cgtggcgcca cggccctgga gctcatggtc     1020

ctcaacgtgc cccggctgat gacccaggac tgcctgcagc agtcacggaa ggtgggagac     1080

tccccaaata tcacggagta catgttctgt gccggctact cggatggcag caaggactcc     1140

tgcaaggggg acagtggagg cccacatgcc acccactacc ggggcacgtg gtacctgacc     1200

ggcatcgtga gctggggcca gggctgcgcc accgtgggcc acttcggcgt gtacaccagg     1260

gtgtcccagt acatcgagtg gctgcagaaa ctgatgagaa gcgagcccag acccggcgtg     1320

ctgctgagag cccccttccc cagcagcagc tccaaggccc ctccccctag cctgcccagc     1380

cctagcagac tgcctgggcc cagtgacacc cctatcctgc ctcagtccag ctccagcaag     1440

gccccacccc ctagcctgcc ttctccttct cggctgcctg gccccagcga tactccaatt     1500

ctgccccagt cctccagcag taaggctccc cctccatctc tgccatcccc cagcagactg     1560

ccaggccctt ctgatacacc catcctccca cagtgatgag gatccgcggc cgcttaatta     1620

a                                                                     1621


<210>  5
<211>  528
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-Modified Factor VII

<400>  5

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 
1               5                   10                  15      


Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val 
            20                  25                  30          


Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro 
        35                  40                  45              


Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu 
    50                  55                  60                  


Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile 
65                  70                  75                  80  


Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly 
                85                  90                  95      


Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro 
            100                 105                 110         


Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 
        115                 120                 125             


Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr 
    130                 135                 140                 


Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala 
145                 150                 155                 160 


Asp Gly Val Ser Cys Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile 
                165                 170                 175     


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


Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 
        195                 200                 205             


Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 
    210                 215                 220                 


Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 
225                 230                 235                 240 


Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 
                245                 250                 255     


Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 
            260                 265                 270         


Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 
        275                 280                 285             


Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 
    290                 295                 300                 


Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 
305                 310                 315                 320 


Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 
                325                 330                 335     


Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser 
            340                 345                 350         


Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 
        355                 360                 365             


Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 
    370                 375                 380                 


Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val 
385                 390                 395                 400 


Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 
                405                 410                 415     


Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 
            420                 425                 430         


Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro Ser Ser Ser Ser 
        435                 440                 445             


Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro 
    450                 455                 460                 


Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro 
465                 470                 475                 480 


Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro 
                485                 490                 495     


Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro 
            500                 505                 510         


Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
        515                 520                 525             


<210>  6
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Signal Sequence

<400>  6

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 
1               5                   10                  15      


Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val 
            20                  25                  30          


Leu His Arg Arg Arg Arg 
        35              


<210>  7
<211>  490
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP- Modified Factor VII

<400>  7

Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro Gly Ser Leu Glu Arg Glu 
1               5                   10                  15      


Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe Lys 
            20                  25                  30          


Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly Asp 
        35                  40                  45              


Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp Gln 
    50                  55                  60                  


Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg Asn 
65                  70                  75                  80  


Cys Glu Thr His Lys Asp Asp Gln Leu Ile Cys Val Asn Glu Asn Gly 
                85                  90                  95      


Gly Cys Glu Gln Tyr Cys Ser Asp His Thr Gly Thr Lys Arg Ser Cys 
            100                 105                 110         


Arg Cys His Glu Gly Tyr Ser Leu Leu Ala Asp Gly Val Ser Cys Thr 
        115                 120                 125             


Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys Arg 
    130                 135                 140                 


Asn Ala Ser Lys Pro Gln Gly Arg Ile Val Gly Gly Lys Val Cys Pro 
145                 150                 155                 160 


Lys Gly Glu Cys Pro Trp Gln Val Leu Leu Leu Val Asn Gly Ala Gln 
                165                 170                 175     


Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile Trp Val Val Ser Ala Ala 
            180                 185                 190         


His Cys Phe Asp Lys Ile Lys Asn Trp Arg Asn Leu Ile Ala Val Leu 
        195                 200                 205             


Gly Glu His Asp Leu Ser Glu His Asp Gly Asp Glu Gln Ser Arg Arg 
    210                 215                 220                 


Val Ala Gln Val Ile Ile Pro Ser Thr Tyr Val Pro Gly Thr Thr Asn 
225                 230                 235                 240 


His Asp Ile Ala Leu Leu Arg Leu His Gln Pro Val Val Leu Thr Asp 
                245                 250                 255     


His Val Val Pro Leu Cys Leu Pro Glu Arg Thr Phe Ser Glu Arg Thr 
            260                 265                 270         


Leu Ala Phe Val Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu 
        275                 280                 285             


Asp Arg Gly Ala Thr Ala Leu Glu Leu Met Val Leu Asn Val Pro Arg 
    290                 295                 300                 


Leu Met Thr Gln Asp Cys Leu Gln Gln Ser Arg Lys Val Gly Asp Ser 
305                 310                 315                 320 


Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala Gly Tyr Ser Asp Gly Ser 
                325                 330                 335     


Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly Pro His Ala Thr His Tyr 
            340                 345                 350         


Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val Ser Trp Gly Gln Gly Cys 
        355                 360                 365             


Ala Thr Val Gly His Phe Gly Val Tyr Thr Arg Val Ser Gln Tyr Ile 
    370                 375                 380                 


Glu Trp Leu Gln Lys Leu Met Arg Ser Glu Pro Arg Pro Gly Val Leu 
385                 390                 395                 400 


Leu Arg Ala Pro Phe Pro Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
                405                 410                 415     


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
            420                 425                 430         


Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro 
        435                 440                 445             


Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser 
    450                 455                 460                 


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
465                 470                 475                 480 


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
                485                 490 


<210>  8
<211>  152
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-Modified Factor VII - Light Chain

<400>  8

Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro Gly Ser Leu Glu Arg Glu 
1               5                   10                  15      


Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe Lys 
            20                  25                  30          


Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly Asp 
        35                  40                  45              


Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp Gln 
    50                  55                  60                  


Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg Asn 
65                  70                  75                  80  


Cys Glu Thr His Lys Asp Asp Gln Leu Ile Cys Val Asn Glu Asn Gly 
                85                  90                  95      


Gly Cys Glu Gln Tyr Cys Ser Asp His Thr Gly Thr Lys Arg Ser Cys 
            100                 105                 110         


Arg Cys His Glu Gly Tyr Ser Leu Leu Ala Asp Gly Val Ser Cys Thr 
        115                 120                 125             


Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys Arg 
    130                 135                 140                 


Asn Ala Ser Lys Pro Gln Gly Arg 
145                 150         


<210>  9
<211>  338
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP-Modified Factor VII - Heavy Chain

<400>  9

Ile Val Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val 
1               5                   10                  15      


Leu Leu Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn 
            20                  25                  30          


Thr Ile Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn 
        35                  40                  45              


Trp Arg Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His 
    50                  55                  60                  


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


Thr Tyr Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu 
                85                  90                  95      


His Gln Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro 
            100                 105                 110         


Glu Arg Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu 
        115                 120                 125             


Val Ser Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu 
    130                 135                 140                 


Leu Met Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln 
145                 150                 155                 160 


Gln Ser Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe 
                165                 170                 175     


Cys Ala Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser 
            180                 185                 190         


Gly Gly Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly 
        195                 200                 205             


Ile Val Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val 
    210                 215                 220                 


Tyr Thr Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg 
225                 230                 235                 240 


Ser Glu Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro Ser Ser 
                245                 250                 255     


Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro 
            260                 265                 270         


Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala 
        275                 280                 285             


Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp 
    290                 295                 300                 


Thr Pro Ile Leu Pro Gln Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser 
305                 310                 315                 320 


Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu 
                325                 330                 335     


Pro Gln 
        


<210>  10
<211>  2413
<212>  DNA
<213>  Homo sapiens

<400>  10
tctagagtcg accccgccat ggagctgagg ccctggttgc tatgggtggt agcagcaaca       60

ggaaccttgg tcctgctagc agctgatgct cagggccaga aggtcttcac caacacgtgg      120

gctgtgcgca tccctggagg cccagcggtg gccaacagtg tggcacggaa gcatgggttc      180

ctcaacctgg gccagatctt cggggactat taccacttct ggcatcgagg agtgacgaag      240

cggtccctgt cgcctcaccg cccgcggcac agccggctgc agagggagcc tcaagtacag      300

tggctggaac agcaggtggc aaagcgacgg actaaacggg acgtgtacca ggagcccaca      360

gaccccaagt ttcctcagca gtggtacctg tctggtgtca ctcagcggga cctgaatgtg      420

aaggcggcct gggcgcaggg ctacacaggg cacggcattg tggtctccat tctggacgat      480

ggcatcgaga agaaccaccc ggacttggca ggcaattatg atcctggggc cagttttgat      540

gtcaatgacc aggaccctga cccccagcct cggtacacac agatgaatga caacaggcac      600

ggcacacggt gtgcggggga agtggctgcg gtggccaaca acggtgtctg tggtgtaggt      660

gtggcctaca acgcccgcat tggaggggtg cgcatgctgg atggcgaggt gacagatgca      720

gtggaggcac gctcgctggg cctgaacccc aaccacatcc acatctacag tgccagctgg      780

ggccccgagg atgacggcaa gacagtggat gggccagccc gcctcgccga ggaggccttc      840

ttccgtgggg ttagccaggg ccgagggggg ctgggctcca tctttgtctg ggcctcgggg      900

aacgggggcc gggaacatga cagctgcaac tgcgacggct acaccaacag tatctacacg      960

ctgtccatca gcagcgccac gcagtttggc aacgtgccgt ggtacagcga ggcctgctcg     1020

tccacactgg ccacgaccta cagcagtggc aaccagaatg agaagcagat cgtgacgact     1080

gacttgcggc agaagtgcac ggagtctcac acgggcacct cagcctctgc ccccttagca     1140

gccggcatca ttgctctcac cctggaggcc aataagaacc tcacatggcg ggacatgcaa     1200

cacctggtgg tacagacctc gaagccagcc cacctcaatg ccaacgactg ggccaccaat     1260

ggtgtgggcc ggaaagtgag ccactcatat ggctacgggc ttttggacgc aggcgccatg     1320

gtggccctgg cccagaattg gaccacagtg gccccccagc ggaagtgcat catcgacatc     1380

ctcaccgagc ccaaagacat cgggaaacgg ctcgaggtgc ggaagaccgt gaccgcgtgc     1440

ctgggcgagc ccaaccacat cactcggctg gagcacgctc aggcgcggct caccctgtcc     1500

tataatcgcc gtggcgacct ggccatccac ctggtcagcc ccatgggcac ccgctccacc     1560

ctgctggcag ccaggccaca tgactactcc gcagatgggt ttaatgactg ggccttcatg     1620

acaactcatt cctgggatga ggatccctct ggcgagtggg tcctagagat tgaaaacacc     1680

agcgaagcca acaactatgg gacgctgacc aagttcaccc tcgtactcta tggcaccgcc     1740

cctgaggggc tgcccgtacc tccagaaagc agtggctgca agaccctcac gtccagtcag     1800

gcctgtgtgg tgtgcgagga aggcttctcc ctgcaccaga agagctgtgt ccagcactgc     1860

cctccaggct tcgcccccca agtcctcgat acgcactata gcaccgagaa tgacgtggag     1920

accatccggg ccagcgtctg cgccccctgc cacgcctcat gtgccacatg ccaggggccg     1980

gccctgacag actgcctcag ctgccccagc cacgcctcct tggaccctgt ggagcagact     2040

tgctcccggc aaagccagag cagccgagag tccccgccac agcagcagcc acctcggctg     2100

cccccggagg tggaggcggg gcaacggctg cgggcagggc tgctgccctc acacctgcct     2160

gaggtggtgg ccggcctcag ctgcgccttc atcgtgctgg tcttcgtcac tgtcttcctg     2220

gtcctgcagc tgcgctctgg ctttagtttt cggggggtga aggtgtacac catggaccgt     2280

ggcctcatct cctacaaggg gctgccccct gaagcctggc aggaggagtg cccgtctgac     2340

tcagaagagg acgagggccg gggcgagagg accgccttta tcaaagacca gagcgccctc     2400

tgaacgcggc cgc                                                        2413


<210>  11
<211>  793
<212>  PRT
<213>  Homo sapiens

<400>  11

Met Glu Leu Arg Pro Trp Leu Leu Trp Val Val Ala Ala Thr Gly Thr 
1               5                   10                  15      


Leu Val Leu Leu Ala Ala Asp Ala Gln Gly Gln Lys Val Phe Thr Asn 
            20                  25                  30          


Thr Trp Ala Val Arg Ile Pro Gly Gly Pro Ala Val Ala Asn Ser Val 
        35                  40                  45              


Ala Arg Lys His Gly Phe Leu Asn Leu Gly Gln Ile Phe Gly Asp Tyr 
    50                  55                  60                  


Tyr His Phe Trp His Arg Gly Val Thr Lys Arg Ser Leu Ser Pro His 
65                  70                  75                  80  


Arg Pro Arg His Ser Arg Leu Gln Arg Glu Pro Gln Val Gln Trp Leu 
                85                  90                  95      


Glu Gln Gln Val Ala Lys Arg Arg Thr Lys Arg Asp Val Tyr Gln Glu 
            100                 105                 110         


Pro Thr Asp Pro Lys Phe Pro Gln Gln Trp Tyr Leu Ser Gly Val Thr 
        115                 120                 125             


Gln Arg Asp Leu Asn Val Lys Ala Ala Trp Ala Gln Gly Tyr Thr Gly 
    130                 135                 140                 


His Gly Ile Val Val Ser Ile Leu Asp Asp Gly Ile Glu Lys Asn His 
145                 150                 155                 160 


Pro Asp Leu Ala Gly Asn Tyr Asp Pro Gly Ala Ser Phe Asp Val Asn 
                165                 170                 175     


Asp Gln Asp Pro Asp Pro Gln Pro Arg Tyr Thr Gln Met Asn Asp Asn 
            180                 185                 190         


Arg His Gly Thr Arg Cys Ala Gly Glu Val Ala Ala Val Ala Asn Asn 
        195                 200                 205             


Gly Val Cys Gly Val Gly Val Ala Tyr Asn Ala Arg Ile Gly Gly Val 
    210                 215                 220                 


Arg Met Leu Asp Gly Glu Val Thr Asp Ala Val Glu Ala Arg Ser Leu 
225                 230                 235                 240 


Gly Leu Asn Pro Asn His Ile His Ile Tyr Ser Ala Ser Trp Gly Pro 
                245                 250                 255     


Glu Asp Asp Gly Lys Thr Val Asp Gly Pro Ala Arg Leu Ala Glu Glu 
            260                 265                 270         


Ala Phe Phe Arg Gly Val Ser Gln Gly Arg Gly Gly Leu Gly Ser Ile 
        275                 280                 285             


Phe Val Trp Ala Ser Gly Asn Gly Gly Arg Glu His Asp Ser Cys Asn 
    290                 295                 300                 


Cys Asp Gly Tyr Thr Asn Ser Ile Tyr Thr Leu Ser Ile Ser Ser Ala 
305                 310                 315                 320 


Thr Gln Phe Gly Asn Val Pro Trp Tyr Ser Glu Ala Cys Ser Ser Thr 
                325                 330                 335     


Leu Ala Thr Thr Tyr Ser Ser Gly Asn Gln Asn Glu Lys Gln Ile Val 
            340                 345                 350         


Thr Thr Asp Leu Arg Gln Lys Cys Thr Glu Ser His Thr Gly Thr Ser 
        355                 360                 365             


Ala Ser Ala Pro Leu Ala Ala Gly Ile Ile Ala Leu Thr Leu Glu Ala 
    370                 375                 380                 


Asn Lys Asn Leu Thr Trp Arg Asp Met Gln His Leu Val Val Gln Thr 
385                 390                 395                 400 


Ser Lys Pro Ala His Leu Asn Ala Asn Asp Trp Ala Thr Asn Gly Val 
                405                 410                 415     


Gly Arg Lys Val Ser His Ser Tyr Gly Tyr Gly Leu Leu Asp Ala Gly 
            420                 425                 430         


Ala Met Val Ala Leu Ala Gln Asn Trp Thr Thr Val Ala Pro Gln Arg 
        435                 440                 445             


Lys Cys Ile Ile Asp Ile Leu Thr Glu Pro Lys Asp Ile Gly Lys Arg 
    450                 455                 460                 


Leu Glu Val Arg Lys Thr Val Thr Ala Cys Leu Gly Glu Pro Asn His 
465                 470                 475                 480 


Ile Thr Arg Leu Glu His Ala Gln Ala Arg Leu Thr Leu Ser Tyr Asn 
                485                 490                 495     


Arg Arg Gly Asp Leu Ala Ile His Leu Val Ser Pro Met Gly Thr Arg 
            500                 505                 510         


Ser Thr Leu Leu Ala Ala Arg Pro His Asp Tyr Ser Ala Asp Gly Phe 
        515                 520                 525             


Asn Asp Trp Ala Phe Met Thr Thr His Ser Trp Asp Glu Asp Pro Ser 
    530                 535                 540                 


Gly Glu Trp Val Leu Glu Ile Glu Asn Thr Ser Glu Ala Asn Asn Tyr 
545                 550                 555                 560 


Gly Thr Leu Thr Lys Phe Thr Leu Val Leu Tyr Gly Thr Ala Pro Glu 
                565                 570                 575     


Gly Leu Pro Val Pro Pro Glu Ser Ser Gly Cys Lys Thr Leu Thr Ser 
            580                 585                 590         


Ser Gln Ala Cys Val Val Cys Glu Glu Gly Phe Ser Leu His Gln Lys 
        595                 600                 605             


Ser Cys Val Gln His Cys Pro Pro Gly Phe Ala Pro Gln Val Leu Asp 
    610                 615                 620                 


Thr His Tyr Ser Thr Glu Asn Asp Val Glu Thr Ile Arg Ala Ser Val 
625                 630                 635                 640 


Cys Ala Pro Cys His Ala Ser Cys Ala Thr Cys Gln Gly Pro Ala Leu 
                645                 650                 655     


Thr Asp Cys Leu Ser Cys Pro Ser His Ala Ser Leu Asp Pro Val Glu 
            660                 665                 670         


Gln Thr Cys Ser Arg Gln Ser Gln Ser Ser Arg Glu Ser Pro Pro Gln 
        675                 680                 685             


Gln Gln Pro Pro Arg Leu Pro Pro Glu Val Glu Ala Gly Gln Arg Leu 
    690                 695                 700                 


Arg Ala Gly Leu Leu Pro Ser His Leu Pro Glu Val Val Ala Gly Leu 
705                 710                 715                 720 


Ser Cys Ala Phe Ile Val Leu Val Phe Val Thr Val Phe Leu Val Leu 
                725                 730                 735     


Gln Leu Arg Ser Gly Phe Ser Phe Arg Gly Val Lys Val Tyr Thr Met 
            740                 745                 750         


Asp Arg Gly Leu Ile Ser Tyr Lys Gly Leu Pro Pro Glu Ala Trp Gln 
        755                 760                 765             


Glu Glu Cys Pro Ser Asp Ser Glu Glu Asp Glu Gly Arg Gly Glu Arg 
    770                 775                 780                 


Thr Ala Phe Ile Lys Asp Gln Ser Ala 
785                 790             


<210>  12
<211>  32
<212>  PRT
<213>  Homo sapiens

<400>  12

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>  13
<211>  28
<212>  PRT
<213>  Homo sapiens

<400>  13

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>  14
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  14

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


<210>  15
<211>  10
<212>  PRT
<213>  Homo sapiens

<400>  15

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


