                         SEQUENCE LISTING

<110>  UCL Business plc
 
<120>  Optimised Coding Sequence and Promoter

<130>  P524906PCT

<150>  GB 0911870.4
<151>  2009-07-08

<160>  21    

<170>  PatentIn version 3.5

<210>  1
<211>  4890
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Codon optimised modified factor VIII nucleotide sequence


<220>
<221>  CDS
<222>  (1)..(4890)

<400>  1
atg cag att gag ctg agc acc tgc ttc ttc ctg tgc ctg ctg agg ttc         48
Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe           
1               5                   10                  15                

tgc ttc tct gcc acc agg aga tac tac ctg ggg gct gtg gag ctg agc         96
Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser           
            20                  25                  30                    

tgg gac tac atg cag tct gac ctg ggg gag ctg cct gtg gat gcc agg        144
Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg           
        35                  40                  45                        

ttc ccc ccc aga gtg ccc aag agc ttc ccc ttc aac acc tct gtg gtg        192
Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val           
    50                  55                  60                            

tac aag aag acc ctg ttt gtg gag ttc act gac cac ctg ttc aac att        240
Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile           
65                  70                  75                  80            

gcc aag ccc agg ccc ccc tgg atg ggc ctg ctg ggc ccc acc atc cag        288
Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln           
                85                  90                  95                

gct gag gtg tat gac act gtg gtg atc acc ctg aag aac atg gcc agc        336
Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser           
            100                 105                 110                   

cac cct gtg agc ctg cat gct gtg ggg gtg agc tac tgg aag gcc tct        384
His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser           
        115                 120                 125                       

gag ggg gct gag tat gat gac cag acc agc cag agg gag aag gag gat        432
Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp           
    130                 135                 140                           

gac aag gtg ttc cct ggg ggc agc cac acc tat gtg tgg cag gtg ctg        480
Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu           
145                 150                 155                 160           

aag gag aat ggc ccc atg gcc tct gac ccc ctg tgc ctg acc tac agc        528
Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser           
                165                 170                 175               

tac ctg agc cat gtg gac ctg gtg aag gac ctg aac tct ggc ctg att        576
Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile           
            180                 185                 190                   

ggg gcc ctg ctg gtg tgc agg gag ggc agc ctg gcc aag gag aag acc        624
Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr           
        195                 200                 205                       

cag acc ctg cac aag ttc atc ctg ctg ttt gct gtg ttt gat gag ggc        672
Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly           
    210                 215                 220                           

aag agc tgg cac tct gaa acc aag aac agc ctg atg cag gac agg gat        720
Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp           
225                 230                 235                 240           

gct gcc tct gcc agg gcc tgg ccc aag atg cac act gtg aat ggc tat        768
Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr           
                245                 250                 255               

gtg aac agg agc ctg cct ggc ctg att ggc tgc cac agg aag tct gtg        816
Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val           
            260                 265                 270                   

tac tgg cat gtg att ggc atg ggc acc acc cct gag gtg cac agc atc        864
Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile           
        275                 280                 285                       

ttc ctg gag ggc cac acc ttc ctg gtc agg aac cac agg cag gcc agc        912
Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser           
    290                 295                 300                           

ctg gag atc agc ccc atc acc ttc ctg act gcc cag acc ctg ctg atg        960
Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met           
305                 310                 315                 320           

gac ctg ggc cag ttc ctg ctg ttc tgc cac atc agc agc cac cag cat       1008
Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His           
                325                 330                 335               

gat ggc atg gag gcc tat gtg aag gtg gac agc tgc cct gag gag ccc       1056
Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro           
            340                 345                 350                   

cag ctg agg atg aag aac aat gag gag gct gag gac tat gat gat gac       1104
Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp           
        355                 360                 365                       

ctg act gac tct gag atg gat gtg gtg agg ttt gat gat gac aac agc       1152
Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser           
    370                 375                 380                           

ccc agc ttc atc cag atc agg tct gtg gcc aag aag cac ccc aag acc       1200
Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr           
385                 390                 395                 400           

tgg gtg cac tac att gct gct gag gag gag gac tgg gac tat gcc ccc       1248
Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro           
                405                 410                 415               

ctg gtg ctg gcc cct gat gac agg agc tac aag agc cag tac ctg aac       1296
Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn           
            420                 425                 430                   

aat ggc ccc cag agg att ggc agg aag tac aag aag gtc agg ttc atg       1344
Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met           
        435                 440                 445                       

gcc tac act gat gaa acc ttc aag acc agg gag gcc atc cag cat gag       1392
Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu           
    450                 455                 460                           

tct ggc atc ctg ggc ccc ctg ctg tat ggg gag gtg ggg gac acc ctg       1440
Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu           
465                 470                 475                 480           

ctg atc atc ttc aag aac cag gcc agc agg ccc tac aac atc tac ccc       1488
Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro           
                485                 490                 495               

cat ggc atc act gat gtg agg ccc ctg tac agc agg agg ctg ccc aag       1536
His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys           
            500                 505                 510                   

ggg gtg aag cac ctg aag gac ttc ccc atc ctg cct ggg gag atc ttc       1584
Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe           
        515                 520                 525                       

aag tac aag tgg act gtg act gtg gag gat ggc ccc acc aag tct gac       1632
Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp           
    530                 535                 540                           

ccc agg tgc ctg acc aga tac tac agc agc ttt gtg aac atg gag agg       1680
Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg           
545                 550                 555                 560           

gac ctg gcc tct ggc ctg att ggc ccc ctg ctg atc tgc tac aag gag       1728
Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu           
                565                 570                 575               

tct gtg gac cag agg ggc aac cag atc atg tct gac aag agg aat gtg       1776
Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val           
            580                 585                 590                   

atc ctg ttc tct gtg ttt gat gag aac agg agc tgg tac ctg act gag       1824
Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu           
        595                 600                 605                       

aac atc cag agg ttc ctg ccc aac cct gct ggg gtg cag ctg gag gac       1872
Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp           
    610                 615                 620                           

cct gag ttc cag gcc agc aac atc atg cac agc atc aat ggc tat gtg       1920
Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val           
625                 630                 635                 640           

ttt gac agc ctg cag ctg tct gtg tgc ctg cat gag gtg gcc tac tgg       1968
Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp           
                645                 650                 655               

tac atc ctg agc att ggg gcc cag act gac ttc ctg tct gtg ttc ttc       2016
Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe           
            660                 665                 670                   

tct ggc tac acc ttc aag cac aag atg gtg tat gag gac acc ctg acc       2064
Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr           
        675                 680                 685                       

ctg ttc ccc ttc tct ggg gag act gtg ttc atg agc atg gag aac cct       2112
Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro           
    690                 695                 700                           

ggc ctg tgg att ctg ggc tgc cac aac tct gac ttc agg aac agg ggc       2160
Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly           
705                 710                 715                 720           

atg act gcc ctg ctg aaa gtc tcc agc tgt gac aag aac act ggg gac       2208
Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp           
                725                 730                 735               

tac tat gag gac agc tat gag gac atc tct gcc tac ctg ctg agc aag       2256
Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys           
            740                 745                 750                   

aac aat gcc att gag ccc agg agc ttc agc cag aac agc agg cac ccc       2304
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro           
        755                 760                 765                       

agc acc agg cag aag cag ttc aat gcc acc acc atc cct gag aat gac       2352
Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp           
    770                 775                 780                           

ata gag aag aca gac cca tgg ttt gcc cac cgg acc ccc atg ccc aag       2400
Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys           
785                 790                 795                 800           

atc cag aat gtg agc agc tct gac ctg ctg atg ctg ctg agg cag agc       2448
Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser           
                805                 810                 815               

ccc acc ccc cat ggc ctg agc ctg tct gac ctg cag gag gcc aag tat       2496
Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr           
            820                 825                 830                   

gaa acc ttc tct gat gac ccc agc cct ggg gcc att gac agc aac aac       2544
Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn           
        835                 840                 845                       

agc ctg tct gag atg acc cac ttc agg ccc cag ctg cac cac tct ggg       2592
Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly           
    850                 855                 860                           

gac atg gtg ttc acc cct gag tct ggc ctg cag ctg agg ctg aat gag       2640
Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu           
865                 870                 875                 880           

aag ctg ggc acc act gct gcc act gag ctg aag aag ctg gac ttc aaa       2688
Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys           
                885                 890                 895               

gtc tcc agc acc agc aac aac ctg atc agc acc atc ccc tct gac aac       2736
Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn           
            900                 905                 910                   

ctg gct gct ggc act gac aac acc agc agc ctg ggc ccc ccc agc atg       2784
Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met           
        915                 920                 925                       

cct gtg cac tat gac agc cag ctg gac acc acc ctg ttt ggc aag aag       2832
Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys           
    930                 935                 940                           

agc agc ccc ctg act gag tct ggg ggc ccc ctg agc ctg tct gag gag       2880
Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu           
945                 950                 955                 960           

aac aat gac agc aag ctg ctg gag tct ggc ctg atg aac agc cag gag       2928
Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu           
                965                 970                 975               

agc agc tgg ggc aag aat gtg agc acc agg agc ttc cag aag aag acc       2976
Ser Ser Trp Gly Lys Asn Val Ser Thr Arg Ser Phe Gln Lys Lys Thr           
            980                 985                 990                   

agg cac tac ttc att gct gct gtg  gag agg ctg tgg gac  tat ggc atg     3024
Arg His Tyr Phe Ile Ala Ala Val  Glu Arg Leu Trp Asp  Tyr Gly Met         
        995                 1000                 1005                     

agc agc  agc ccc cat gtg ctg  agg aac agg gcc cag  tct ggc tct        3069
Ser Ser  Ser Pro His Val Leu  Arg Asn Arg Ala Gln  Ser Gly Ser            
    1010                 1015                 1020                        

gtg ccc  cag ttc aag aag gtg  gtg ttc cag gag ttc  act gat ggc        3114
Val Pro  Gln Phe Lys Lys Val  Val Phe Gln Glu Phe  Thr Asp Gly            
    1025                 1030                 1035                        

agc ttc  acc cag ccc ctg tac  aga ggg gag ctg aat  gag cac ctg        3159
Ser Phe  Thr Gln Pro Leu Tyr  Arg Gly Glu Leu Asn  Glu His Leu            
    1040                 1045                 1050                        

ggc ctg  ctg ggc ccc tac atc  agg gct gag gtg gag  gac aac atc        3204
Gly Leu  Leu Gly Pro Tyr Ile  Arg Ala Glu Val Glu  Asp Asn Ile            
    1055                 1060                 1065                        

atg gtg  acc ttc agg aac cag  gcc agc agg ccc tac  agc ttc tac        3249
Met Val  Thr Phe Arg Asn Gln  Ala Ser Arg Pro Tyr  Ser Phe Tyr            
    1070                 1075                 1080                        

agc agc  ctg atc agc tat gag  gag gac cag agg cag  ggg gct gag        3294
Ser Ser  Leu Ile Ser Tyr Glu  Glu Asp Gln Arg Gln  Gly Ala Glu            
    1085                 1090                 1095                        

ccc agg  aag aac ttt gtg aag  ccc aat gaa acc aag  acc tac ttc        3339
Pro Arg  Lys Asn Phe Val Lys  Pro Asn Glu Thr Lys  Thr Tyr Phe            
    1100                 1105                 1110                        

tgg aag  gtg cag cac cac atg  gcc ccc acc aag gat  gag ttt gac        3384
Trp Lys  Val Gln His His Met  Ala Pro Thr Lys Asp  Glu Phe Asp            
    1115                 1120                 1125                        

tgc aag  gcc tgg gcc tac ttc  tct gat gtg gac ctg  gag aag gat        3429
Cys Lys  Ala Trp Ala Tyr Phe  Ser Asp Val Asp Leu  Glu Lys Asp            
    1130                 1135                 1140                        

gtg cac  tct ggc ctg att ggc  ccc ctg ctg gtg tgc  cac acc aac        3474
Val His  Ser Gly Leu Ile Gly  Pro Leu Leu Val Cys  His Thr Asn            
    1145                 1150                 1155                        

acc ctg  aac cct gcc cat ggc  agg cag gtg act gtg  cag gag ttt        3519
Thr Leu  Asn Pro Ala His Gly  Arg Gln Val Thr Val  Gln Glu Phe            
    1160                 1165                 1170                        

gcc ctg  ttc ttc acc atc ttt  gat gaa acc aag agc  tgg tac ttc        3564
Ala Leu  Phe Phe Thr Ile Phe  Asp Glu Thr Lys Ser  Trp Tyr Phe            
    1175                 1180                 1185                        

act gag  aac atg gag agg aac  tgc agg gcc ccc tgc  aac atc cag        3609
Thr Glu  Asn Met Glu Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln            
    1190                 1195                 1200                        

atg gag  gac ccc acc ttc aag  gag aac tac agg ttc  cat gcc atc        3654
Met Glu  Asp Pro Thr Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile            
    1205                 1210                 1215                        

aat ggc  tac atc atg gac acc  ctg cct ggc ctg gtg  atg gcc cag        3699
Asn Gly  Tyr Ile Met Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln            
    1220                 1225                 1230                        

gac cag  agg atc agg tgg tac  ctg ctg agc atg ggc  agc aat gag        3744
Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu            
    1235                 1240                 1245                        

aac atc  cac agc atc cac ttc  tct ggc cat gtg ttc  act gtg agg        3789
Asn Ile  His Ser Ile His Phe  Ser Gly His Val Phe  Thr Val Arg            
    1250                 1255                 1260                        

aag aag  gag gag tac aag atg  gcc ctg tac aac ctg  tac cct ggg        3834
Lys Lys  Glu Glu Tyr Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly            
    1265                 1270                 1275                        

gtg ttt  gag act gtg gag atg  ctg ccc agc aag gct  ggc atc tgg        3879
Val Phe  Glu Thr Val Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp            
    1280                 1285                 1290                        

agg gtg  gag tgc ctg att ggg  gag cac ctg cat gct  ggc atg agc        3924
Arg Val  Glu Cys Leu Ile Gly  Glu His Leu His Ala  Gly Met Ser            
    1295                 1300                 1305                        

acc ctg  ttc ctg gtg tac agc  aac aag tgc cag acc  ccc ctg ggc        3969
Thr Leu  Phe Leu Val Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly            
    1310                 1315                 1320                        

atg gcc  tct ggc cac atc agg  gac ttc cag atc act  gcc tct ggc        4014
Met Ala  Ser Gly His Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly            
    1325                 1330                 1335                        

cag tat  ggc cag tgg gcc ccc  aag ctg gcc agg ctg  cac tac tct        4059
Gln Tyr  Gly Gln Trp Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser            
    1340                 1345                 1350                        

ggc agc  atc aat gcc tgg agc  acc aag gag ccc ttc  agc tgg atc        4104
Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile            
    1355                 1360                 1365                        

aag gtg  gac ctg ctg gcc ccc  atg atc atc cat ggc  atc aag acc        4149
Lys Val  Asp Leu Leu Ala Pro  Met Ile Ile His Gly  Ile Lys Thr            
    1370                 1375                 1380                        

cag ggg  gcc agg cag aag ttc  agc agc ctg tac atc  agc cag ttc        4194
Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe            
    1385                 1390                 1395                        

atc atc  atg tac agc ctg gat  ggc aag aag tgg cag  acc tac agg        4239
Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg            
    1400                 1405                 1410                        

ggc aac  agc act ggc acc ctg  atg gtg ttc ttt ggc  aat gtg gac        4284
Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe Phe Gly  Asn Val Asp            
    1415                 1420                 1425                        

agc tct  ggc atc aag cac aac  atc ttc aac ccc ccc  atc att gcc        4329
Ser Ser  Gly Ile Lys His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala            
    1430                 1435                 1440                        

aga tac  atc agg ctg cac ccc  acc cac tac agc atc  agg agc acc        4374
Arg Tyr  Ile Arg Leu His Pro  Thr His Tyr Ser Ile  Arg Ser Thr            
    1445                 1450                 1455                        

ctg agg  atg gag ctg atg ggc  tgt gac ctg aac agc  tgc agc atg        4419
Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met            
    1460                 1465                 1470                        

ccc ctg  ggc atg gag agc aag  gcc atc tct gat gcc  cag atc act        4464
Pro Leu  Gly Met Glu Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr            
    1475                 1480                 1485                        

gcc agc  agc tac ttc acc aac  atg ttt gcc acc tgg  agc ccc agc        4509
Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser            
    1490                 1495                 1500                        

aag gcc  agg ctg cac ctg cag  ggc agg agc aat gcc  tgg agg ccc        4554
Lys Ala  Arg Leu His Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro            
    1505                 1510                 1515                        

cag gtc  aac aac ccc aag gag  tgg ctg cag gtg gac  ttc cag aag        4599
Gln Val  Asn Asn Pro Lys Glu  Trp Leu Gln Val Asp  Phe Gln Lys            
    1520                 1525                 1530                        

acc atg  aag gtg act ggg gtg  acc acc cag ggg gtg  aag agc ctg        4644
Thr Met  Lys Val Thr Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu            
    1535                 1540                 1545                        

ctg acc  agc atg tat gtg aag  gag ttc ctg atc agc  agc agc cag        4689
Leu Thr  Ser Met Tyr Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln            
    1550                 1555                 1560                        

gat ggc  cac cag tgg acc ctg  ttc ttc cag aat ggc  aag gtg aag        4734
Asp Gly  His Gln Trp Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys            
    1565                 1570                 1575                        

gtg ttc  cag ggc aac cag gac  agc ttc acc cct gtg  gtg aac agc        4779
Val Phe  Gln Gly Asn Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser            
    1580                 1585                 1590                        

ctg gac  ccc ccc ctg ctg acc  aga tac ctg agg att  cac ccc cag        4824
Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln            
    1595                 1600                 1605                        

agc tgg  gtg cac cag att gcc  ctg agg atg gag gtg  ctg ggc tgt        4869
Ser Trp  Val His Gln Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys            
    1610                 1615                 1620                        

gag gcc  cag gac ctg tac tga                                          4890
Glu Ala  Gln Asp Leu Tyr                                                  
    1625                                                                  


<210>  2
<211>  1629
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII protein

<400>  2

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


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


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


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


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


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


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu 
                565                 570                 575     


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
    770                 775                 780                 


Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys 
785                 790                 795                 800 


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
                805                 810                 815     


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
            820                 825                 830         


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
        835                 840                 845             


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
    850                 855                 860                 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
865                 870                 875                 880 


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
                885                 890                 895     


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
            900                 905                 910         


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
        915                 920                 925             


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
    930                 935                 940                 


Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu 
945                 950                 955                 960 


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
                965                 970                 975     


Ser Ser Trp Gly Lys Asn Val Ser Thr Arg Ser Phe Gln Lys Lys Thr 
            980                 985                 990         


Arg His Tyr Phe Ile Ala Ala Val  Glu Arg Leu Trp Asp  Tyr Gly Met 
        995                 1000                 1005             


Ser Ser  Ser Pro His Val Leu  Arg Asn Arg Ala Gln  Ser Gly Ser 
    1010                 1015                 1020             


Val Pro  Gln Phe Lys Lys Val  Val Phe Gln Glu Phe  Thr Asp Gly 
    1025                 1030                 1035             


Ser Phe  Thr Gln Pro Leu Tyr  Arg Gly Glu Leu Asn  Glu His Leu 
    1040                 1045                 1050             


Gly Leu  Leu Gly Pro Tyr Ile  Arg Ala Glu Val Glu  Asp Asn Ile 
    1055                 1060                 1065             


Met Val  Thr Phe Arg Asn Gln  Ala Ser Arg Pro Tyr  Ser Phe Tyr 
    1070                 1075                 1080             


Ser Ser  Leu Ile Ser Tyr Glu  Glu Asp Gln Arg Gln  Gly Ala Glu 
    1085                 1090                 1095             


Pro Arg  Lys Asn Phe Val Lys  Pro Asn Glu Thr Lys  Thr Tyr Phe 
    1100                 1105                 1110             


Trp Lys  Val Gln His His Met  Ala Pro Thr Lys Asp  Glu Phe Asp 
    1115                 1120                 1125             


Cys Lys  Ala Trp Ala Tyr Phe  Ser Asp Val Asp Leu  Glu Lys Asp 
    1130                 1135                 1140             


Val His  Ser Gly Leu Ile Gly  Pro Leu Leu Val Cys  His Thr Asn 
    1145                 1150                 1155             


Thr Leu  Asn Pro Ala His Gly  Arg Gln Val Thr Val  Gln Glu Phe 
    1160                 1165                 1170             


Ala Leu  Phe Phe Thr Ile Phe  Asp Glu Thr Lys Ser  Trp Tyr Phe 
    1175                 1180                 1185             


Thr Glu  Asn Met Glu Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln 
    1190                 1195                 1200             


Met Glu  Asp Pro Thr Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile 
    1205                 1210                 1215             


Asn Gly  Tyr Ile Met Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln 
    1220                 1225                 1230             


Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu 
    1235                 1240                 1245             


Asn Ile  His Ser Ile His Phe  Ser Gly His Val Phe  Thr Val Arg 
    1250                 1255                 1260             


Lys Lys  Glu Glu Tyr Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly 
    1265                 1270                 1275             


Val Phe  Glu Thr Val Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp 
    1280                 1285                 1290             


Arg Val  Glu Cys Leu Ile Gly  Glu His Leu His Ala  Gly Met Ser 
    1295                 1300                 1305             


Thr Leu  Phe Leu Val Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly 
    1310                 1315                 1320             


Met Ala  Ser Gly His Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly 
    1325                 1330                 1335             


Gln Tyr  Gly Gln Trp Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser 
    1340                 1345                 1350             


Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile 
    1355                 1360                 1365             


Lys Val  Asp Leu Leu Ala Pro  Met Ile Ile His Gly  Ile Lys Thr 
    1370                 1375                 1380             


Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe 
    1385                 1390                 1395             


Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg 
    1400                 1405                 1410             


Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe Phe Gly  Asn Val Asp 
    1415                 1420                 1425             


Ser Ser  Gly Ile Lys His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala 
    1430                 1435                 1440             


Arg Tyr  Ile Arg Leu His Pro  Thr His Tyr Ser Ile  Arg Ser Thr 
    1445                 1450                 1455             


Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met 
    1460                 1465                 1470             


Pro Leu  Gly Met Glu Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr 
    1475                 1480                 1485             


Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser 
    1490                 1495                 1500             


Lys Ala  Arg Leu His Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro 
    1505                 1510                 1515             


Gln Val  Asn Asn Pro Lys Glu  Trp Leu Gln Val Asp  Phe Gln Lys 
    1520                 1525                 1530             


Thr Met  Lys Val Thr Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu 
    1535                 1540                 1545             


Leu Thr  Ser Met Tyr Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln 
    1550                 1555                 1560             


Asp Gly  His Gln Trp Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys 
    1565                 1570                 1575             


Val Phe  Gln Gly Asn Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser 
    1580                 1585                 1590             


Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln 
    1595                 1600                 1605             


Ser Trp  Val His Gln Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys 
    1610                 1615                 1620             


Glu Ala  Gln Asp Leu Tyr 
    1625                 


<210>  3
<211>  251
<212>  DNA
<213>  Artificial sequence

<220>
<223>  modified promoter sequence

<400>  3
tgtttgctgc ttgcaatgtt tgcccatttt agggtggaca caggacgctg tggtttctga       60

gccagggggc gactcagatc ccagccagtg gacttagccc ctgtttgctc ctccgataac      120

tggggtgacc ttggttaata ttcaccagca gcctcccccg ttgcccctct ggatccactg      180

cttaaatacg gacgaggaca gggccctgtc tcctcagctt caggcaccac cactgacctg      240

ggacagtgaa t                                                           251


<210>  4
<211>  5061
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Codon optimised modified factor VIII nucleotide sequence

<400>  4
atgcagatcg agctgtccac ctgctttttt ctgtgcctgc tgcggttctg cttcagcgcc       60

acccggcggt actacctggg cgccgtggag ctgtcctggg actacatgca gagcgacctg      120

ggcgagctgc ccgtggacgc ccggttcccc cccagagtgc ccaagagctt ccccttcaac      180

accagcgtgg tgtacaagaa aaccctgttc gtggagttca ccgaccacct gttcaatatc      240

gccaagccca ggcccccctg gatgggcctg ctgggcccca ccatccaggc cgaggtgtac      300

gacaccgtgg tgatcaccct gaagaacatg gccagccacc ccgtgagcct gcacgccgtg      360

ggcgtgagct actggaaggc cagcgagggc gccgagtacg acgaccagac cagccagcgg      420

gagaaagaag atgacaaggt gttccctggc ggcagccaca cctacgtgtg gcaggtgctg      480

aaagaaaacg gccccatggc ctccgacccc ctgtgcctga cctacagcta cctgagccac      540

gtggacctgg tgaaggacct gaacagcggc ctgatcggcg ctctgctcgt ctgccgggag      600

ggcagcctgg ccaaagagaa aacccagacc ctgcacaagt tcatcctgct gttcgccgtg      660

ttcgacgagg gcaagagctg gcacagcgag acaaagaaca gcctgatgca ggaccgggac      720

gccgcctctg ccagagcctg gcccaagatg cacaccgtga acggctacgt gaacagaagc      780

ctgcccggcc tgattggctg ccaccggaag agcgtgtact ggcacgtgat cggcatgggc      840

accacacccg aggtgcacag catctttctg gaagggcaca cctttctggt ccggaaccac      900

cggcaggcca gcctggaaat cagccctatc accttcctga ccgcccagac actgctgatg      960

gacctgggcc agttcctgct gttttgccac atcagctctc accagcacga cggcatggaa     1020

gcctacgtga aggtggactc ttgccccgag gaaccccagc tgcggatgaa gaacaacgag     1080

gaagccgagg actacgacga cgacctgacc gacagcgaga tggacgtggt gcggttcgac     1140

gacgacaaca gccccagctt catccagatc agaagcgtgg ccaagaagca ccccaagacc     1200

tgggtgcact atatcgccgc cgaggaagag gactgggact acgcccccct ggtgctggcc     1260

cccgacgaca gaagctacaa gagccagtac ctgaacaatg gcccccagcg gatcggccgg     1320

aagtacaaga aagtgcggtt catggcctac accgacgaga cattcaagac ccgggaggcc     1380

atccagcacg agagcggcat cctgggcccc ctgctgtacg gcgaagtggg cgacacactg     1440

ctgatcatct tcaagaacca ggctagccgg ccctacaaca tctaccccca cggcatcacc     1500

gacgtgcggc ccctgtacag caggcggctg cccaagggcg tgaagcacct gaaggacttc     1560

cccatcctgc ccggcgagat cttcaagtac aagtggaccg tgaccgtgga ggacggcccc     1620

accaagagcg accccagatg cctgacccgg tactacagca gcttcgtgaa catggaacgg     1680

gacctggcct ccgggctgat cggacctctg ctgatctgct acaaagaaag cgtggaccag     1740

cggggcaacc agatcatgag cgacaagcgg aacgtgatcc tgttcagcgt gttcgatgag     1800

aaccggtcct ggtatctgac cgagaacatc cagcggtttc tgcccaaccc tgccggcgtg     1860

cagctggaag atcccgagtt ccaggccagc aacatcatgc actccatcaa tggctacgtg     1920

ttcgactctc tgcagctctc cgtgtgtctg cacgaggtgg cctactggta catcctgagc     1980

atcggcgccc agaccgactt cctgagcgtg ttcttcagcg gctacacctt caagcacaag     2040

atggtgtacg aggacaccct gaccctgttc cctttcagcg gcgagacagt gttcatgagc     2100

atggaaaacc ccggcctgtg gattctgggc tgccacaaca gcgacttccg gaaccggggc     2160

atgaccgccc tgctgaaggt gtccagctgc gacaagaaca ccggcgacta ctacgaggac     2220

agctacgagg atatcagcgc ctacctgctg tccaagaaca acgccatcga accccggagc     2280

ttcagccaga acccccccgt gctgacgcgt agcttcagcc agaacagccg gcaccccagc     2340

acccggcaga agcagttcaa cgccaccacc atccccgaga acgacatcga gaaaaccgac     2400

ccttggtttg cccaccggac ccccatgccc aagatccaga acgtgtccag cagcgacctg     2460

ctgatgctgc tgcggcagag ccccacccct cacggcctga gcctgagcga cctgcaggaa     2520

gccaagtacg agacattcag cgacgacccc agccctggcg ccatcgacag caacaacagc     2580

ctgtccgaga tgacccactt ccggccccag ctgcaccaca gcggcgacat ggtgttcacc     2640

cccgagagcg gcctgcagct gcggctgaac gagaagctgg gcaccaccgc cgccaccgag     2700

ctgaagaagc tggacttcaa ggtctccagc accagcaaca acctgatcag caccatcccc     2760

agcgacaacc tggccgctgg caccgacaac accagcagcc tgggccctcc cagcatgccc     2820

gtgcactacg acagccagct ggacaccacc ctgttcggca agaagtccag ccccctgacc     2880

gagtccggcg gacccctgtc cctgagcgag gaaaacaacg acagcaagct gctggaaagc     2940

ggcctgatga acagccagga aagcagctgg ggcaagaatg tgtccagcac gcgtcaccag     3000

cgggagatca cccggacaac cctgcagtcc gaccaggaag agatcgatta cgacgacacc     3060

atcagcgtgg agatgaagaa agaggatttc gatatctacg acgaggacga gaaccagagc     3120

cccagaagct tccagaagaa aacccggcac tacttcattg ccgccgtgga gaggctgtgg     3180

gactacggca tgagttctag cccccacgtg ctgcggaacc gggcccagag cggcagcgtg     3240

ccccagttca agaaagtggt gttccaggaa ttcacagacg gcagcttcac ccagcctctg     3300

tatagaggcg agctgaacga gcacctgggg ctgctggggc cctacatcag ggccgaagtg     3360

gaggacaaca tcatggtgac cttccggaat caggccagca gaccctactc cttctacagc     3420

agcctgatca gctacgaaga ggaccagcgg cagggcgccg aaccccggaa gaacttcgtg     3480

aagcccaacg aaaccaagac ctacttctgg aaagtgcagc accacatggc ccccaccaag     3540

gacgagttcg actgcaaggc ctgggcctac ttcagcgacg tggatctgga aaaggacgtg     3600

cactctggac tgattggccc actcctggtc tgccacacta acaccctcaa ccccgcccac     3660

ggccgccagg tgaccgtgca ggaattcgcc ctgttcttca ccatcttcga cgagacaaag     3720

tcctggtact tcaccgagaa tatggaacgg aactgcagag ccccctgcaa catccagatg     3780

gaagatccta ccttcaaaga gaactaccgg ttccacgcca tcaacggcta catcatggac     3840

accctgcctg gcctggtgat ggcccaggac cagagaatcc ggtggtatct gctgtccatg     3900

ggcagcaacg agaatatcca cagcatccac ttcagcggcc acgtgttcac cgtgcggaag     3960

aaagaagagt acaagatggc cctgtacaac ctgtaccccg gcgtgttcga gacagtggag     4020

atgctgccca gcaaggccgg catctggcgg gtggagtgtc tgatcggcga gcacctgcac     4080

gctggcatga gcaccctgtt tctggtgtac agcaacaagt gccagacccc actgggcatg     4140

gcctctggcc acatccggga cttccagatc accgcctccg gccagtacgg ccagtgggcc     4200

cccaagctgg ccagactgca ctacagcggc agcatcaacg cctggtccac caaagagccc     4260

ttcagctgga tcaaggtgga cctgctggcc cctatgatca tccacggcat taagacccag     4320

ggcgccaggc agaagttcag cagcctgtac atcagccagt tcatcatcat gtacagcctg     4380

gacggcaaga agtggcagac ctaccggggc aacagcaccg gcaccctgat ggtgttcttc     4440

ggcaatgtgg acagcagcgg catcaagcac aacatcttca acccccccat cattgcccgg     4500

tacatccggc tgcaccccac ccactacagc attagatcca cactgagaat ggaactgatg     4560

ggctgcgacc tgaactcctg cagcatgcct ctgggcatgg aaagcaaggc catcagcgac     4620

gcccagatca cagccagcag ctacttcacc aacatgttcg ccacctggtc cccctccaag     4680

gccaggctgc acctgcaggg ccggtccaac gcctggcggc ctcaggtcaa caaccccaaa     4740

gaatggctgc aggtggactt tcagaaaacc atgaaggtga ccggcgtgac cacccagggc     4800

gtgaaaagcc tgctgaccag catgtacgtg aaagagtttc tgatcagcag ctctcaggat     4860

ggccaccagt ggaccctgtt ctttcagaac ggcaaggtga aagtgttcca gggcaaccag     4920

gactccttca cccccgtggt gaactccctg gacccccccc tgctgacccg ctacctgaga     4980

atccaccccc agtcttgggt gcaccagatc gccctcagga tggaagtcct gggatgtgag     5040

gcccaggatc tgtactgatg a                                               5061


<210>  5
<211>  4377
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Codon optimised modified factor VIII nucleotide sequence

<400>  5
atgcagatcg agctgtccac ctgctttttt ctgtgcctgc tgcggttctg cttcagcgcc       60

acccggcggt actacctggg cgccgtggag ctgtcctggg actacatgca gagcgacctg      120

ggcgagctgc ccgtggacgc ccggttcccc cccagagtgc ccaagagctt ccccttcaac      180

accagcgtgg tgtacaagaa aaccctgttc gtggagttca ccgaccacct gttcaatatc      240

gccaagccca ggcccccctg gatgggcctg ctgggcccca ccatccaggc cgaggtgtac      300

gacaccgtgg tgatcaccct gaagaacatg gccagccacc ccgtgagcct gcacgccgtg      360

ggcgtgagct actggaaggc cagcgagggc gccgagtacg acgaccagac cagccagcgg      420

gagaaagaag atgacaaggt gttccctggc ggcagccaca cctacgtgtg gcaggtgctg      480

aaagaaaacg gccccatggc ctccgacccc ctgtgcctga cctacagcta cctgagccac      540

gtggacctgg tgaaggacct gaacagcggc ctgatcggcg ctctgctcgt ctgccgggag      600

ggcagcctgg ccaaagagaa aacccagacc ctgcacaagt tcatcctgct gttcgccgtg      660

ttcgacgagg gcaagagctg gcacagcgag acaaagaaca gcctgatgca ggaccgggac      720

gccgcctctg ccagagcctg gcccaagatg cacaccgtga acggctacgt gaacagaagc      780

ctgcccggcc tgattggctg ccaccggaag agcgtgtact ggcacgtgat cggcatgggc      840

accacacccg aggtgcacag catctttctg gaagggcaca cctttctggt ccggaaccac      900

cggcaggcca gcctggaaat cagccctatc accttcctga ccgcccagac actgctgatg      960

gacctgggcc agttcctgct gttttgccac atcagctctc accagcacga cggcatggaa     1020

gcctacgtga aggtggactc ttgccccgag gaaccccagc tgcggatgaa gaacaacgag     1080

gaagccgagg actacgacga cgacctgacc gacagcgaga tggacgtggt gcggttcgac     1140

gacgacaaca gccccagctt catccagatc agaagcgtgg ccaagaagca ccccaagacc     1200

tgggtgcact atatcgccgc cgaggaagag gactgggact acgcccccct ggtgctggcc     1260

cccgacgaca gaagctacaa gagccagtac ctgaacaatg gcccccagcg gatcggccgg     1320

aagtacaaga aagtgcggtt catggcctac accgacgaga cattcaagac ccgggaggcc     1380

atccagcacg agagcggcat cctgggcccc ctgctgtacg gcgaagtggg cgacacactg     1440

ctgatcatct tcaagaacca ggctagccgg ccctacaaca tctaccccca cggcatcacc     1500

gacgtgcggc ccctgtacag caggcggctg cccaagggcg tgaagcacct gaaggacttc     1560

cccatcctgc ccggcgagat cttcaagtac aagtggaccg tgaccgtgga ggacggcccc     1620

accaagagcg accccagatg cctgacccgg tactacagca gcttcgtgaa catggaacgg     1680

gacctggcct ccgggctgat cggacctctg ctgatctgct acaaagaaag cgtggaccag     1740

cggggcaacc agatcatgag cgacaagcgg aacgtgatcc tgttcagcgt gttcgatgag     1800

aaccggtcct ggtatctgac cgagaacatc cagcggtttc tgcccaaccc tgccggcgtg     1860

cagctggaag atcccgagtt ccaggccagc aacatcatgc actccatcaa tggctacgtg     1920

ttcgactctc tgcagctctc cgtgtgtctg cacgaggtgg cctactggta catcctgagc     1980

atcggcgccc agaccgactt cctgagcgtg ttcttcagcg gctacacctt caagcacaag     2040

atggtgtacg aggacaccct gaccctgttc cctttcagcg gcgagacagt gttcatgagc     2100

atggaaaacc ccggcctgtg gattctgggc tgccacaaca gcgacttccg gaaccggggc     2160

atgaccgccc tgctgaaggt gtccagctgc gacaagaaca ccggcgacta ctacgaggac     2220

agctacgagg atatcagcgc ctacctgctg tccaagaaca acgccatcga accccggagc     2280

ttcagccaga acccccccgt gctgacgcgt caccagcggg agatcacccg gacaaccctg     2340

cagtccgacc aggaagagat cgattacgac gacaccatca gcgtggagat gaagaaagag     2400

gatttcgata tctacgacga ggacgagaac cagagcccca gaagcttcca gaagaaaacc     2460

cggcactact tcattgccgc cgtggagagg ctgtgggact acggcatgag ttctagcccc     2520

cacgtgctgc ggaaccgggc ccagagcggc agcgtgcccc agttcaagaa agtggtgttc     2580

caggaattca cagacggcag cttcacccag cctctgtata gaggcgagct gaacgagcac     2640

ctggggctgc tggggcccta catcagggcc gaagtggagg acaacatcat ggtgaccttc     2700

cggaatcagg ccagcagacc ctactccttc tacagcagcc tgatcagcta cgaagaggac     2760

cagcggcagg gcgccgaacc ccggaagaac ttcgtgaagc ccaacgaaac caagacctac     2820

ttctggaaag tgcagcacca catggccccc accaaggacg agttcgactg caaggcctgg     2880

gcctacttca gcgacgtgga tctggaaaag gacgtgcact ctggactgat tggcccactc     2940

ctggtctgcc acactaacac cctcaacccc gcccacggcc gccaggtgac cgtgcaggaa     3000

ttcgccctgt tcttcaccat cttcgacgag acaaagtcct ggtacttcac cgagaatatg     3060

gaacggaact gcagagcccc ctgcaacatc cagatggaag atcctacctt caaagagaac     3120

taccggttcc acgccatcaa cggctacatc atggacaccc tgcctggcct ggtgatggcc     3180

caggaccaga gaatccggtg gtatctgctg tccatgggca gcaacgagaa tatccacagc     3240

atccacttca gcggccacgt gttcaccgtg cggaagaaag aagagtacaa gatggccctg     3300

tacaacctgt accccggcgt gttcgagaca gtggagatgc tgcccagcaa ggccggcatc     3360

tggcgggtgg agtgtctgat cggcgagcac ctgcacgctg gcatgagcac cctgtttctg     3420

gtgtacagca acaagtgcca gaccccactg ggcatggcct ctggccacat ccgggacttc     3480

cagatcaccg cctccggcca gtacggccag tgggccccca agctggccag actgcactac     3540

agcggcagca tcaacgcctg gtccaccaaa gagcccttca gctggatcaa ggtggacctg     3600

ctggccccta tgatcatcca cggcattaag acccagggcg ccaggcagaa gttcagcagc     3660

ctgtacatca gccagttcat catcatgtac agcctggacg gcaagaagtg gcagacctac     3720

cggggcaaca gcaccggcac cctgatggtg ttcttcggca atgtggacag cagcggcatc     3780

aagcacaaca tcttcaaccc ccccatcatt gcccggtaca tccggctgca ccccacccac     3840

tacagcatta gatccacact gagaatggaa ctgatgggct gcgacctgaa ctcctgcagc     3900

atgcctctgg gcatggaaag caaggccatc agcgacgccc agatcacagc cagcagctac     3960

ttcaccaaca tgttcgccac ctggtccccc tccaaggcca ggctgcacct gcagggccgg     4020

tccaacgcct ggcggcctca ggtcaacaac cccaaagaat ggctgcaggt ggactttcag     4080

aaaaccatga aggtgaccgg cgtgaccacc cagggcgtga aaagcctgct gaccagcatg     4140

tacgtgaaag agtttctgat cagcagctct caggatggcc accagtggac cctgttcttt     4200

cagaacggca aggtgaaagt gttccagggc aaccaggact ccttcacccc cgtggtgaac     4260

tccctggacc cccccctgct gacccgctac ctgagaatcc acccccagtc ttgggtgcac     4320

cagatcgccc tcaggatgga agtcctggga tgtgaggccc aggatctgta ctgatga        4377


<210>  6
<211>  4980
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Codon optimised modified factor VIII nucleotide sequence

<400>  6
atgcagatcg agctgtccac ctgctttttt ctgtgcctgc tgcggttctg cttcagcgcc       60

acccggcggt actacctggg cgccgtggag ctgtcctggg actacatgca gagcgacctg      120

ggcgagctgc ccgtggacgc ccggttcccc cccagagtgc ccaagagctt ccccttcaac      180

accagcgtgg tgtacaagaa aaccctgttc gtggagttca ccgaccacct gttcaatatc      240

gccaagccca ggcccccctg gatgggcctg ctgggcccca ccatccaggc cgaggtgtac      300

gacaccgtgg tgatcaccct gaagaacatg gccagccacc ccgtgagcct gcacgccgtg      360

ggcgtgagct actggaaggc cagcgagggc gccgagtacg acgaccagac cagccagcgg      420

gagaaagaag atgacaaggt gttccctggc ggcagccaca cctacgtgtg gcaggtgctg      480

aaagaaaacg gccccatggc ctccgacccc ctgtgcctga cctacagcta cctgagccac      540

gtggacctgg tgaaggacct gaacagcggc ctgatcggcg ctctgctcgt ctgccgggag      600

ggcagcctgg ccaaagagaa aacccagacc ctgcacaagt tcatcctgct gttcgccgtg      660

ttcgacgagg gcaagagctg gcacagcgag acaaagaaca gcctgatgca ggaccgggac      720

gccgcctctg ccagagcctg gcccaagatg cacaccgtga acggctacgt gaacagaagc      780

ctgcccggcc tgattggctg ccaccggaag agcgtgtact ggcacgtgat cggcatgggc      840

accacacccg aggtgcacag catctttctg gaagggcaca cctttctggt ccggaaccac      900

cggcaggcca gcctggaaat cagccctatc accttcctga ccgcccagac actgctgatg      960

gacctgggcc agttcctgct gttttgccac atcagctctc accagcacga cggcatggaa     1020

gcctacgtga aggtggactc ttgccccgag gaaccccagc tgcggatgaa gaacaacgag     1080

gaagccgagg actacgacga cgacctgacc gacagcgaga tggacgtggt gcggttcgac     1140

gacgacaaca gccccagctt catccagatc agaagcgtgg ccaagaagca ccccaagacc     1200

tgggtgcact atatcgccgc cgaggaagag gactgggact acgcccccct ggtgctggcc     1260

cccgacgaca gaagctacaa gagccagtac ctgaacaatg gcccccagcg gatcggccgg     1320

aagtacaaga aagtgcggtt catggcctac accgacgaga cattcaagac ccgggaggcc     1380

atccagcacg agagcggcat cctgggcccc ctgctgtacg gcgaagtggg cgacacactg     1440

ctgatcatct tcaagaacca ggctagccgg ccctacaaca tctaccccca cggcatcacc     1500

gacgtgcggc ccctgtacag caggcggctg cccaagggcg tgaagcacct gaaggacttc     1560

cccatcctgc ccggcgagat cttcaagtac aagtggaccg tgaccgtgga ggacggcccc     1620

accaagagcg accccagatg cctgacccgg tactacagca gcttcgtgaa catggaacgg     1680

gacctggcct ccgggctgat cggacctctg ctgatctgct acaaagaaag cgtggaccag     1740

cggggcaacc agatcatgag cgacaagcgg aacgtgatcc tgttcagcgt gttcgatgag     1800

aaccggtcct ggtatctgac cgagaacatc cagcggtttc tgcccaaccc tgccggcgtg     1860

cagctggaag atcccgagtt ccaggccagc aacatcatgc actccatcaa tggctacgtg     1920

ttcgactctc tgcagctctc cgtgtgtctg cacgaggtgg cctactggta catcctgagc     1980

atcggcgccc agaccgactt cctgagcgtg ttcttcagcg gctacacctt caagcacaag     2040

atggtgtacg aggacaccct gaccctgttc cctttcagcg gcgagacagt gttcatgagc     2100

atggaaaacc ccggcctgtg gattctgggc tgccacaaca gcgacttccg gaaccggggc     2160

atgaccgccc tgctgaaggt gtccagctgc gacaagaaca ccggcgacta ctacgaggac     2220

agctacgagg atatcagcgc ctacctgctg tccaagaaca acgccatcga accccggagc     2280

ttcagccaga acccccccgt gctgacgcgt ggcatgcggc ccagaaacca caccgtgctg     2340

ctgaaagtgt gcaacaaggt gcccatcaac aacagcaccc acagcgtgaa caccagcacc     2400

ctgaacgcca ccgacggcag gcggtgctac ctgaagaagg tgaccctgac cccccctggc     2460

ggcgaggacg ccaacatcac ctctggcgag cgcatccccg aggacatcct ggaagagctg     2520

cagctggatg gcgaagtgac agccgcccct tccggcatcc tgagagtggg cgagcaggcc     2580

ctgcggcgga gaaggcaggc cgaggacaac tccaccgact tcgacatcta cagcggcgac     2640

gagggcggcg aagagcggag cgagatccag gaacgcccag ccgagaaccg gaccaccgcc     2700

aacgccaccg gcatcaaccg gaccaaagag ctggaagagg gcaacgagat cctgctgacc     2760

ggcaaccccg gcaacagcaa gcggagcttc accgtggagc ccgtgaccag cgaggaaatg     2820

gtgcagaact acatcatgtc tgaggaagag aagctgaagc cccaccatca gcagcccggc     2880

aacgtggccg tgaacgagct gtctgtgacg cgtcaccagc gggagatcac ccggacaacc     2940

ctgcagtccg accaggaaga gatcgattac gacgacacca tcagcgtgga gatgaagaaa     3000

gaggatttcg atatctacga cgaggacgag aaccagagcc ccagaagctt ccagaagaaa     3060

acccggcact acttcattgc cgccgtggag aggctgtggg actacggcat gagttctagc     3120

ccccacgtgc tgcggaaccg ggcccagagc ggcagcgtgc cccagttcaa gaaagtggtg     3180

ttccaggaat tcacagacgg cagcttcacc cagcctctgt atagaggcga gctgaacgag     3240

cacctggggc tgctggggcc ctacatcagg gccgaagtgg aggacaacat catggtgacc     3300

ttccggaatc aggccagcag accctactcc ttctacagca gcctgatcag ctacgaagag     3360

gaccagcggc agggcgccga accccggaag aacttcgtga agcccaacga aaccaagacc     3420

tacttctgga aagtgcagca ccacatggcc cccaccaagg acgagttcga ctgcaaggcc     3480

tgggcctact tcagcgacgt ggatctggaa aaggacgtgc actctggact gattggccca     3540

ctcctggtct gccacactaa caccctcaac cccgcccacg gccgccaggt gaccgtgcag     3600

gaattcgccc tgttcttcac catcttcgac gagacaaagt cctggtactt caccgagaat     3660

atggaacgga actgcagagc cccctgcaac atccagatgg aagatcctac cttcaaagag     3720

aactaccggt tccacgccat caacggctac atcatggaca ccctgcctgg cctggtgatg     3780

gcccaggacc agagaatccg gtggtatctg ctgtccatgg gcagcaacga gaatatccac     3840

agcatccact tcagcggcca cgtgttcacc gtgcggaaga aagaagagta caagatggcc     3900

ctgtacaacc tgtaccccgg cgtgttcgag acagtggaga tgctgcccag caaggccggc     3960

atctggcggg tggagtgtct gatcggcgag cacctgcacg ctggcatgag caccctgttt     4020

ctggtgtaca gcaacaagtg ccagacccca ctgggcatgg cctctggcca catccgggac     4080

ttccagatca ccgcctccgg ccagtacggc cagtgggccc ccaagctggc cagactgcac     4140

tacagcggca gcatcaacgc ctggtccacc aaagagccct tcagctggat caaggtggac     4200

ctgctggccc ctatgatcat ccacggcatt aagacccagg gcgccaggca gaagttcagc     4260

agcctgtaca tcagccagtt catcatcatg tacagcctgg acggcaagaa gtggcagacc     4320

taccggggca acagcaccgg caccctgatg gtgttcttcg gcaatgtgga cagcagcggc     4380

atcaagcaca acatcttcaa cccccccatc attgcccggt acatccggct gcaccccacc     4440

cactacagca ttagatccac actgagaatg gaactgatgg gctgcgacct gaactcctgc     4500

agcatgcctc tgggcatgga aagcaaggcc atcagcgacg cccagatcac agccagcagc     4560

tacttcacca acatgttcgc cacctggtcc ccctccaagg ccaggctgca cctgcagggc     4620

cggtccaacg cctggcggcc tcaggtcaac aaccccaaag aatggctgca ggtggacttt     4680

cagaaaacca tgaaggtgac cggcgtgacc acccagggcg tgaaaagcct gctgaccagc     4740

atgtacgtga aagagtttct gatcagcagc tctcaggatg gccaccagtg gaccctgttc     4800

tttcagaacg gcaaggtgaa agtgttccag ggcaaccagg actccttcac ccccgtggtg     4860

aactccctgg acccccccct gctgacccgc tacctgagaa tccaccccca gtcttgggtg     4920

caccagatcg ccctcaggat ggaagtcctg ggatgtgagg cccaggatct gtactgatga     4980


<210>  7
<211>  5336
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Codon optimised modified factor VIII nucleotide sequence

<400>  7
tgtttgctgc ttgcaatgtt tgcccatttt agggtggaca caggacgctg tggtttctga       60

gccagggggc gactcagatc ccagccagtg gacttagccc ctgtttgctc ctccgataac      120

tggggtgacc ttggttaata ttcaccagca gcctcccccg ttgcccctct ggatccactg      180

cttaaatacg gacgaggaca gggccctgtc tcctcagctt caggcaccac cactgacctg      240

ggacagtgaa tcgcggccgc caccatgcag attgagctga gcacctgctt cttcctgtgc      300

ctgctgaggt tctgcttctc tgccaccagg agatactacc tgggggctgt ggagctgagc      360

tgggactaca tgcagtctga cctgggggag ctgcctgtgg atgccaggtt cccccccaga      420

gtgcccaaga gcttcccctt caacacctct gtggtgtaca agaagaccct gtttgtggag      480

ttcactgacc acctgttcaa cattgccaag cccaggcccc cctggatggg cctgctgggc      540

cccaccatcc aggctgaggt gtatgacact gtggtgatca ccctgaagaa catggccagc      600

caccctgtga gcctgcatgc tgtgggggtg agctactgga aggcctctga gggggctgag      660

tatgatgacc agaccagcca gagggagaag gaggatgaca aggtgttccc tgggggcagc      720

cacacctatg tgtggcaggt gctgaaggag aatggcccca tggcctctga ccccctgtgc      780

ctgacctaca gctacctgag ccatgtggac ctggtgaagg acctgaactc tggcctgatt      840

ggggccctgc tggtgtgcag ggagggcagc ctggccaagg agaagaccca gaccctgcac      900

aagttcatcc tgctgtttgc tgtgtttgat gagggcaaga gctggcactc tgaaaccaag      960

aacagcctga tgcaggacag ggatgctgcc tctgccaggg cctggcccaa gatgcacact     1020

gtgaatggct atgtgaacag gagcctgcct ggcctgattg gctgccacag gaagtctgtg     1080

tactggcatg tgattggcat gggcaccacc cctgaggtgc acagcatctt cctggagggc     1140

cacaccttcc tggtcaggaa ccacaggcag gccagcctgg agatcagccc catcaccttc     1200

ctgactgccc agaccctgct gatggacctg ggccagttcc tgctgttctg ccacatcagc     1260

agccaccagc atgatggcat ggaggcctat gtgaaggtgg acagctgccc tgaggagccc     1320

cagctgagga tgaagaacaa tgaggaggct gaggactatg atgatgacct gactgactct     1380

gagatggatg tggtgaggtt tgatgatgac aacagcccca gcttcatcca gatcaggtct     1440

gtggccaaga agcaccccaa gacctgggtg cactacattg ctgctgagga ggaggactgg     1500

gactatgccc ccctggtgct ggcccctgat gacaggagct acaagagcca gtacctgaac     1560

aatggccccc agaggattgg caggaagtac aagaaggtca ggttcatggc ctacactgat     1620

gaaaccttca agaccaggga ggccatccag catgagtctg gcatcctggg ccccctgctg     1680

tatggggagg tgggggacac cctgctgatc atcttcaaga accaggccag caggccctac     1740

aacatctacc cccatggcat cactgatgtg aggcccctgt acagcaggag gctgcccaag     1800

ggggtgaagc acctgaagga cttccccatc ctgcctgggg agatcttcaa gtacaagtgg     1860

actgtgactg tggaggatgg ccccaccaag tctgacccca ggtgcctgac cagatactac     1920

agcagctttg tgaacatgga gagggacctg gcctctggcc tgattggccc cctgctgatc     1980

tgctacaagg agtctgtgga ccagaggggc aaccagatca tgtctgacaa gaggaatgtg     2040

atcctgttct ctgtgtttga tgagaacagg agctggtacc tgactgagaa catccagagg     2100

ttcctgccca accctgctgg ggtgcagctg gaggaccctg agttccaggc cagcaacatc     2160

atgcacagca tcaatggcta tgtgtttgac agcctgcagc tgtctgtgtg cctgcatgag     2220

gtggcctact ggtacatcct gagcattggg gcccagactg acttcctgtc tgtgttcttc     2280

tctggctaca ccttcaagca caagatggtg tatgaggaca ccctgaccct gttccccttc     2340

tctggggaga ctgtgttcat gagcatggag aaccctggcc tgtggattct gggctgccac     2400

aactctgact tcaggaacag gggcatgact gccctgctga aagtctccag ctgtgacaag     2460

aacactgggg actactatga ggacagctat gaggacatct ctgcctacct gctgagcaag     2520

aacaatgcca ttgagcccag gagcttcagc cagaacagca ggcaccccag caccaggcag     2580

aagcagttca atgccaccac catccctgag aatgacatag agaagacaga cccatggttt     2640

gcccaccgga cccccatgcc caagatccag aatgtgagca gctctgacct gctgatgctg     2700

ctgaggcaga gccccacccc ccatggcctg agcctgtctg acctgcagga ggccaagtat     2760

gaaaccttct ctgatgaccc cagccctggg gccattgaca gcaacaacag cctgtctgag     2820

atgacccact tcaggcccca gctgcaccac tctggggaca tggtgttcac ccctgagtct     2880

ggcctgcagc tgaggctgaa tgagaagctg ggcaccactg ctgccactga gctgaagaag     2940

ctggacttca aagtctccag caccagcaac aacctgatca gcaccatccc ctctgacaac     3000

ctggctgctg gcactgacaa caccagcagc ctgggccccc ccagcatgcc tgtgcactat     3060

gacagccagc tggacaccac cctgtttggc aagaagagca gccccctgac tgagtctggg     3120

ggccccctga gcctgtctga ggagaacaat gacagcaagc tgctggagtc tggcctgatg     3180

aacagccagg agagcagctg gggcaagaat gtgagcagca gggagatcac caggaccacc     3240

ctgcagtctg accaggagga gattgactat gatgacacca tctctgtgga gatgaagaag     3300

gaggactttg acatctacga cgaggacgag aaccagagcc ccaggagctt ccagaagaag     3360

accaggcact acttcattgc tgctgtggag aggctgtggg actatggcat gagcagcagc     3420

ccccatgtgc tgaggaacag ggcccagtct ggctctgtgc cccagttcaa gaaggtggtg     3480

ttccaggagt tcactgatgg cagcttcacc cagcccctgt acagagggga gctgaatgag     3540

cacctgggcc tgctgggccc ctacatcagg gctgaggtgg aggacaacat catggtgacc     3600

ttcaggaacc aggccagcag gccctacagc ttctacagca gcctgatcag ctatgaggag     3660

gaccagaggc agggggctga gcccaggaag aactttgtga agcccaatga aaccaagacc     3720

tacttctgga aggtgcagca ccacatggcc cccaccaagg atgagtttga ctgcaaggcc     3780

tgggcctact tctctgatgt ggacctggag aaggatgtgc actctggcct gattggcccc     3840

ctgctggtgt gccacaccaa caccctgaac cctgcccatg gcaggcaggt gactgtgcag     3900

gagtttgccc tgttcttcac catctttgat gaaaccaaga gctggtactt cactgagaac     3960

atggagagga actgcagggc cccctgcaac atccagatgg aggaccccac cttcaaggag     4020

aactacaggt tccatgccat caatggctac atcatggaca ccctgcctgg cctggtgatg     4080

gcccaggacc agaggatcag gtggtacctg ctgagcatgg gcagcaatga gaacatccac     4140

agcatccact tctctggcca tgtgttcact gtgaggaaga aggaggagta caagatggcc     4200

ctgtacaacc tgtaccctgg ggtgtttgag actgtggaga tgctgcccag caaggctggc     4260

atctggaggg tggagtgcct gattggggag cacctgcatg ctggcatgag caccctgttc     4320

ctggtgtaca gcaacaagtg ccagaccccc ctgggcatgg cctctggcca catcagggac     4380

ttccagatca ctgcctctgg ccagtatggc cagtgggccc ccaagctggc caggctgcac     4440

tactctggca gcatcaatgc ctggagcacc aaggagccct tcagctggat caaggtggac     4500

ctgctggccc ccatgatcat ccatggcatc aagacccagg gggccaggca gaagttcagc     4560

agcctgtaca tcagccagtt catcatcatg tacagcctgg atggcaagaa gtggcagacc     4620

tacaggggca acagcactgg caccctgatg gtgttctttg gcaatgtgga cagctctggc     4680

atcaagcaca acatcttcaa cccccccatc attgccagat acatcaggct gcaccccacc     4740

cactacagca tcaggagcac cctgaggatg gagctgatgg gctgtgacct gaacagctgc     4800

agcatgcccc tgggcatgga gagcaaggcc atctctgatg cccagatcac tgccagcagc     4860

tacttcacca acatgtttgc cacctggagc cccagcaagg ccaggctgca cctgcagggc     4920

aggagcaatg cctggaggcc ccaggtcaac aaccccaagg agtggctgca ggtggacttc     4980

cagaagacca tgaaggtgac tggggtgacc acccaggggg tgaagagcct gctgaccagc     5040

atgtatgtga aggagttcct gatcagcagc agccaggatg gccaccagtg gaccctgttc     5100

ttccagaatg gcaaggtgaa ggtgttccag ggcaaccagg acagcttcac ccctgtggtg     5160

aacagcctgg acccccccct gctgaccaga tacctgagga ttcaccccca gagctgggtg     5220

caccagattg ccctgaggat ggaggtgctg ggctgtgagg cccaggacct gtactgatcg     5280

cgaataaaag atctttattt tcattagatc tgtgtgttgg ttttttgtgt gatgca         5336


<210>  8
<211>  42
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic construct

<400>  8
agcttcagcc agaacccccc cgtgctgacg cgtcaccagc gg                          42


<210>  9
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  9
tgtgtgcccg tctgttgtgt                                                   20


<210>  10
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  10
gagtcctgcg tcgagagagc                                                   20


<210>  11
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  11
cgcccgaaca gggacttgaa                                                   20


<210>  12
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  12
aaaacgagca gtgacctgag g                                                 21


<210>  13
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  13
ttcagtcatg ctgctagcgc                                                   20


<210>  14
<211>  22
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  14
tgcacggaat ctcgtctcag tc                                                22


<210>  15
<211>  25
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  15
tcacccacaa gttgcccatc tacga                                             25


<210>  16
<211>  25
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  16
cagcggaacc gctcattgcc aatgg                                             25


<210>  17
<211>  26
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer

<400>  17
atgccctccc ccatgccatc ctgcgt                                            26


<210>  18
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic construct

<400>  18

Ser Phe Ser Gln Asn Pro Pro Val Leu Thr Arg His Gln Arg 
1               5                   10                  


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

<220>
<223>  Synthetic construct

<400>  19

Ser Phe Ser Gln Asn Pro Pro Val Leu Thr Arg 
1               5                   10      


<210>  20
<211>  5
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic construct

<400>  20

Thr Arg His Gln Arg 
1               5   


<210>  21
<211>  1670
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII protein

<400>  21

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


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


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


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


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


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


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu 
                565                 570                 575     


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
    770                 775                 780                 


Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys 
785                 790                 795                 800 


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
                805                 810                 815     


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
            820                 825                 830         


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
        835                 840                 845             


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
    850                 855                 860                 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
865                 870                 875                 880 


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
                885                 890                 895     


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
            900                 905                 910         


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
        915                 920                 925             


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
    930                 935                 940                 


Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu 
945                 950                 955                 960 


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
                965                 970                 975     


Ser Ser Trp Gly Lys Asn Val Ser Ser Arg Glu Ile Thr Arg Thr Thr 
            980                 985                 990         


Leu Gln Ser Asp Gln Glu Glu Ile  Asp Tyr Asp Asp Thr  Ile Ser Val 
        995                 1000                 1005             


Glu Met  Lys Lys Glu Asp Phe  Asp Ile Tyr Asp Glu  Asp Glu Asn 
    1010                 1015                 1020             


Gln Ser  Pro Arg Ser Phe Gln  Lys Lys Thr Arg His  Tyr Phe Ile 
    1025                 1030                 1035             


Ala Ala  Val Glu Arg Leu Trp  Asp Tyr Gly Met Ser  Ser Ser Pro 
    1040                 1045                 1050             


His Val  Leu Arg Asn Arg Ala  Gln Ser Gly Ser Val  Pro Gln Phe 
    1055                 1060                 1065             


Lys Lys  Val Val Phe Gln Glu  Phe Thr Asp Gly Ser  Phe Thr Gln 
    1070                 1075                 1080             


Pro Leu  Tyr Arg Gly Glu Leu  Asn Glu His Leu Gly  Leu Leu Gly 
    1085                 1090                 1095             


Pro Tyr  Ile Arg Ala Glu Val  Glu Asp Asn Ile Met  Val Thr Phe 
    1100                 1105                 1110             


Arg Asn  Gln Ala Ser Arg Pro  Tyr Ser Phe Tyr Ser  Ser Leu Ile 
    1115                 1120                 1125             


Ser Tyr  Glu Glu Asp Gln Arg  Gln Gly Ala Glu Pro  Arg Lys Asn 
    1130                 1135                 1140             


Phe Val  Lys Pro Asn Glu Thr  Lys Thr Tyr Phe Trp  Lys Val Gln 
    1145                 1150                 1155             


His His  Met Ala Pro Thr Lys  Asp Glu Phe Asp Cys  Lys Ala Trp 
    1160                 1165                 1170             


Ala Tyr  Phe Ser Asp Val Asp  Leu Glu Lys Asp Val  His Ser Gly 
    1175                 1180                 1185             


Leu Ile  Gly Pro Leu Leu Val  Cys His Thr Asn Thr  Leu Asn Pro 
    1190                 1195                 1200             


Ala His  Gly Arg Gln Val Thr  Val Gln Glu Phe Ala  Leu Phe Phe 
    1205                 1210                 1215             


Thr Ile  Phe Asp Glu Thr Lys  Ser Trp Tyr Phe Thr  Glu Asn Met 
    1220                 1225                 1230             


Glu Arg  Asn Cys Arg Ala Pro  Cys Asn Ile Gln Met  Glu Asp Pro 
    1235                 1240                 1245             


Thr Phe  Lys Glu Asn Tyr Arg  Phe His Ala Ile Asn  Gly Tyr Ile 
    1250                 1255                 1260             


Met Asp  Thr Leu Pro Gly Leu  Val Met Ala Gln Asp  Gln Arg Ile 
    1265                 1270                 1275             


Arg Trp  Tyr Leu Leu Ser Met  Gly Ser Asn Glu Asn  Ile His Ser 
    1280                 1285                 1290             


Ile His  Phe Ser Gly His Val  Phe Thr Val Arg Lys  Lys Glu Glu 
    1295                 1300                 1305             


Tyr Lys  Met Ala Leu Tyr Asn  Leu Tyr Pro Gly Val  Phe Glu Thr 
    1310                 1315                 1320             


Val Glu  Met Leu Pro Ser Lys  Ala Gly Ile Trp Arg  Val Glu Cys 
    1325                 1330                 1335             


Leu Ile  Gly Glu His Leu His  Ala Gly Met Ser Thr  Leu Phe Leu 
    1340                 1345                 1350             


Val Tyr  Ser Asn Lys Cys Gln  Thr Pro Leu Gly Met  Ala Ser Gly 
    1355                 1360                 1365             


His Ile  Arg Asp Phe Gln Ile  Thr Ala Ser Gly Gln  Tyr Gly Gln 
    1370                 1375                 1380             


Trp Ala  Pro Lys Leu Ala Arg  Leu His Tyr Ser Gly  Ser Ile Asn 
    1385                 1390                 1395             


Ala Trp  Ser Thr Lys Glu Pro  Phe Ser Trp Ile Lys  Val Asp Leu 
    1400                 1405                 1410             


Leu Ala  Pro Met Ile Ile His  Gly Ile Lys Thr Gln  Gly Ala Arg 
    1415                 1420                 1425             


Gln Lys  Phe Ser Ser Leu Tyr  Ile Ser Gln Phe Ile  Ile Met Tyr 
    1430                 1435                 1440             


Ser Leu  Asp Gly Lys Lys Trp  Gln Thr Tyr Arg Gly  Asn Ser Thr 
    1445                 1450                 1455             


Gly Thr  Leu Met Val Phe Phe  Gly Asn Val Asp Ser  Ser Gly Ile 
    1460                 1465                 1470             


Lys His  Asn Ile Phe Asn Pro  Pro Ile Ile Ala Arg  Tyr Ile Arg 
    1475                 1480                 1485             


Leu His  Pro Thr His Tyr Ser  Ile Arg Ser Thr Leu  Arg Met Glu 
    1490                 1495                 1500             


Leu Met  Gly Cys Asp Leu Asn  Ser Cys Ser Met Pro  Leu Gly Met 
    1505                 1510                 1515             


Glu Ser  Lys Ala Ile Ser Asp  Ala Gln Ile Thr Ala  Ser Ser Tyr 
    1520                 1525                 1530             


Phe Thr  Asn Met Phe Ala Thr  Trp Ser Pro Ser Lys  Ala Arg Leu 
    1535                 1540                 1545             


His Leu  Gln Gly Arg Ser Asn  Ala Trp Arg Pro Gln  Val Asn Asn 
    1550                 1555                 1560             


Pro Lys  Glu Trp Leu Gln Val  Asp Phe Gln Lys Thr  Met Lys Val 
    1565                 1570                 1575             


Thr Gly  Val Thr Thr Gln Gly  Val Lys Ser Leu Leu  Thr Ser Met 
    1580                 1585                 1590             


Tyr Val  Lys Glu Phe Leu Ile  Ser Ser Ser Gln Asp  Gly His Gln 
    1595                 1600                 1605             


Trp Thr  Leu Phe Phe Gln Asn  Gly Lys Val Lys Val  Phe Gln Gly 
    1610                 1615                 1620             


Asn Gln  Asp Ser Phe Thr Pro  Val Val Asn Ser Leu  Asp Pro Pro 
    1625                 1630                 1635             


Leu Leu  Thr Arg Tyr Leu Arg  Ile His Pro Gln Ser  Trp Val His 
    1640                 1645                 1650             


Gln Ile  Ala Leu Arg Met Glu  Val Leu Gly Cys Glu  Ala Gln Asp 
    1655                 1660                 1665             


Leu Tyr  
    1670 


