               SEQUENCE LISTING

<110> Biotest AG

<120> De-immunized Factor VIII molecule and pharmaceutical compositions comprising the same

<130> 11573 P 6689 EP

<160> 54

<170> BiSSAP 1.3.6

<210> 1
<211> 2351
<212> PRT
<213> Homo sapiens


<220> 
<221> SIGNAL
<222> 1..19
<223> Signal sequence

<220> 
<223> FVIII wt full length

<400> 1
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 Thr Glu Ser Gly Arg Leu Phe 
            980                 985                 990         
Lys Gly Lys Arg Ala His Gly Pro Ala Leu Leu Thr Lys Asp Asn Ala 
        995                 1000                1005            
Leu Phe Lys Val Ser Ile Ser Leu Leu Lys Thr Asn Lys Thr Ser Asn 
    1010                1015                1020                
Asn Ser Ala Thr Asn Arg Lys Thr His Ile Asp Gly Pro Ser Leu Leu 
1025                1030                1035                1040
Ile Glu Asn Ser Pro Ser Val Trp Gln Asn Ile Leu Glu Ser Asp Thr 
                1045                1050                1055    
Glu Phe Lys Lys Val Thr Pro Leu Ile His Asp Arg Met Leu Met Asp 
            1060                1065                1070        
Lys Asn Ala Thr Ala Leu Arg Leu Asn His Met Ser Asn Lys Thr Thr 
        1075                1080                1085            
Ser Ser Lys Asn Met Glu Met Val Gln Gln Lys Lys Glu Gly Pro Ile 
    1090                1095                1100                
Pro Pro Asp Ala Gln Asn Pro Asp Met Ser Phe Phe Lys Met Leu Phe 
1105                1110                1115                1120
Leu Pro Glu Ser Ala Arg Trp Ile Gln Arg Thr His Gly Lys Asn Ser 
                1125                1130                1135    
Leu Asn Ser Gly Gln Gly Pro Ser Pro Lys Gln Leu Val Ser Leu Gly 
            1140                1145                1150        
Pro Glu Lys Ser Val Glu Gly Gln Asn Phe Leu Ser Glu Lys Asn Lys 
        1155                1160                1165            
Val Val Val Gly Lys Gly Glu Phe Thr Lys Asp Val Gly Leu Lys Glu 
    1170                1175                1180                
Met Val Phe Pro Ser Ser Arg Asn Leu Phe Leu Thr Asn Leu Asp Asn 
1185                1190                1195                1200
Leu His Glu Asn Asn Thr His Asn Gln Glu Lys Lys Ile Gln Glu Glu 
                1205                1210                1215    
Ile Glu Lys Lys Glu Thr Leu Ile Gln Glu Asn Val Val Leu Pro Gln 
            1220                1225                1230        
Ile His Thr Val Thr Gly Thr Lys Asn Phe Met Lys Asn Leu Phe Leu 
        1235                1240                1245            
Leu Ser Thr Arg Gln Asn Val Glu Gly Ser Tyr Asp Gly Ala Tyr Ala 
    1250                1255                1260                
Pro Val Leu Gln Asp Phe Arg Ser Leu Asn Asp Ser Thr Asn Arg Thr 
1265                1270                1275                1280
Lys Lys His Thr Ala His Phe Ser Lys Lys Gly Glu Glu Glu Asn Leu 
                1285                1290                1295    
Glu Gly Leu Gly Asn Gln Thr Lys Gln Ile Val Glu Lys Tyr Ala Cys 
            1300                1305                1310        
Thr Thr Arg Ile Ser Pro Asn Thr Ser Gln Gln Asn Phe Val Thr Gln 
        1315                1320                1325            
Arg Ser Lys Arg Ala Leu Lys Gln Phe Arg Leu Pro Leu Glu Glu Thr 
    1330                1335                1340                
Glu Leu Glu Lys Arg Ile Ile Val Asp Asp Thr Ser Thr Gln Trp Ser 
1345                1350                1355                1360
Lys Asn Met Lys His Leu Thr Pro Ser Thr Leu Thr Gln Ile Asp Tyr 
                1365                1370                1375    
Asn Glu Lys Glu Lys Gly Ala Ile Thr Gln Ser Pro Leu Ser Asp Cys 
            1380                1385                1390        
Leu Thr Arg Ser His Ser Ile Pro Gln Ala Asn Arg Ser Pro Leu Pro 
        1395                1400                1405            
Ile Ala Lys Val Ser Ser Phe Pro Ser Ile Arg Pro Ile Tyr Leu Thr 
    1410                1415                1420                
Arg Val Leu Phe Gln Asp Asn Ser Ser His Leu Pro Ala Ala Ser Tyr 
1425                1430                1435                1440
Arg Lys Lys Asp Ser Gly Val Gln Glu Ser Ser His Phe Leu Gln Gly 
                1445                1450                1455    
Ala Lys Lys Asn Asn Leu Ser Leu Ala Ile Leu Thr Leu Glu Met Thr 
            1460                1465                1470        
Gly Asp Gln Arg Glu Val Gly Ser Leu Gly Thr Ser Ala Thr Asn Ser 
        1475                1480                1485            
Val Thr Tyr Lys Lys Val Glu Asn Thr Val Leu Pro Lys Pro Asp Leu 
    1490                1495                1500                
Pro Lys Thr Ser Gly Lys Val Glu Leu Leu Pro Lys Val His Ile Tyr 
1505                1510                1515                1520
Gln Lys Asp Leu Phe Pro Thr Glu Thr Ser Asn Gly Ser Pro Gly His 
                1525                1530                1535    
Leu Asp Leu Val Glu Gly Ser Leu Leu Gln Gly Thr Glu Gly Ala Ile 
            1540                1545                1550        
Lys Trp Asn Glu Ala Asn Arg Pro Gly Lys Val Pro Phe Leu Arg Val 
        1555                1560                1565            
Ala Thr Glu Ser Ser Ala Lys Thr Pro Ser Lys Leu Leu Asp Pro Leu 
    1570                1575                1580                
Ala Trp Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys 
1585                1590                1595                1600
Ser Gln Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr 
                1605                1610                1615    
Ile Leu Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile 
            1620                1625                1630        
Asn Glu Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln 
        1635                1640                1645            
Gly Arg Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg 
    1650                1655                1660                
His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu 
1665                1670                1675                1680
Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe 
                1685                1690                1695    
Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys 
            1700                1705                1710        
Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr 
        1715                1720                1725            
Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly 
    1730                1735                1740                
Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly 
1745                1750                1755                1760
Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly 
                1765                1770                1775    
Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val 
            1780                1785                1790        
Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu 
        1795                1800                1805            
Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn 
    1810                1815                1820                
Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His 
1825                1830                1835                1840
His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr 
                1845                1850                1855    
Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly 
            1860                1865                1870        
Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg 
        1875                1880                1885            
Gln Val Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu 
    1890                1895                1900                
Thr Lys Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala 
1905                1910                1915                1920
Pro Cys Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg 
                1925                1930                1935    
Phe His Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val 
            1940                1945                1950        
Met Ala Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser 
        1955                1960                1965            
Asn Glu Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val 
    1970                1975                1980                
Arg Lys Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly 
1985                1990                1995                2000
Val Phe Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg 
                2005                2010                2015    
Val Glu Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu 
            2020                2025                2030        
Phe Leu Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser 
        2035                2040                2045            
Gly His Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln 
    2050                2055                2060                
Trp Ala Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala 
2065                2070                2075                2080
Trp Ser Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala 
                2085                2090                2095    
Pro Met Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe 
            2100                2105                2110        
Ser Ser Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly 
        2115                2120                2125            
Lys Lys Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val 
    2130                2135                2140                
Phe Phe Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn 
2145                2150                2155                2160
Pro Pro Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser 
                2165                2170                2175    
Ile Arg Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser 
            2180                2185                2190        
Cys Ser Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln 
        2195                2200                2205            
Ile Thr Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro 
    2210                2215                2220                
Ser Lys Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro 
2225                2230                2235                2240
Gln Val Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr 
                2245                2250                2255    
Met Lys Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr 
            2260                2265                2270        
Ser Met Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His 
        2275                2280                2285            
Gln Trp Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly 
    2290                2295                2300                
Asn Gln Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu 
2305                2310                2315                2320
Leu Thr Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile 
                2325                2330                2335    
Ala Leu Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
            2340                2345                2350    

<210> 2
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19
<223> Signal sequence

<220> 
<223> FVIII-6rs - human FVIII B-domain deleted

<220> 
<221> DOMAIN
<222> 20..348
<223> A1

<220> 
<221> DOMAIN
<222> 349..398
<223> a1

<220> 
<221> DOMAIN
<222> 399..730
<223> A2

<220> 
<221> DOMAIN
<222> 731..759
<223> a2

<220> 
<221> DOMAIN
<222> 760..849
<223> truncated B-domain

<220> 
<221> DOMAIN
<222> 850..894
<223> a3

<220> 
<221> DOMAIN
<222> 895..1221
<223> A3

<220> 
<221> DOMAIN
<222> 1222..1374
<223> C1

<220> 
<221> DOMAIN
<222> 1375..1533
<223> C2

<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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 3
<211> 1457
<212> PRT
<213> Artificial Sequence


<220> 
<223> Refacto - human FVIII B-domain deleted

<400> 3
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 Pro Pro Val Leu 
        755                 760                 765             
Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 
Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu 
785                 790                 795                 800 
Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe 
                805                 810                 815     
Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
            820                 825                 830         
Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln 
        835                 840                 845             
Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
    850                 855                 860                 
Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His 
865                 870                 875                 880 
Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile 
                885                 890                 895     
Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
            900                 905                 910         
Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg 
        915                 920                 925             
Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val 
    930                 935                 940                 
Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp 
945                 950                 955                 960 
Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
                965                 970                 975     
Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His 
            980                 985                 990         
Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe 
        995                 1000                1005            
Asp Glu Thr Lys Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys 
    1010                1015                1020                
Arg Ala Pro Cys Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn 
1025                1030                1035                1040
Tyr Arg Phe His Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly 
                1045                1050                1055    
Leu Val Met Ala Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met 
            1060                1065                1070        
Gly Ser Asn Glu Asn Ile His Ser Ile His Phe Ser Gly His Val Phe 
        1075                1080                1085            
Thr Val Arg Lys Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr 
    1090                1095                1100                
Pro Gly Val Phe Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile 
1105                1110                1115                1120
Trp Arg Val Glu Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser 
                1125                1130                1135    
Thr Leu Phe Leu Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met 
            1140                1145                1150        
Ala Ser Gly His Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr 
        1155                1160                1165            
Gly Gln Trp Ala Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile 
    1170                1175                1180                
Asn Ala Trp Ser Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu 
1185                1190                1195                1200
Leu Ala Pro Met Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln 
                1205                1210                1215    
Lys Phe Ser Ser Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu 
            1220                1225                1230        
Asp Gly Lys Lys Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu 
        1235                1240                1245            
Met Val Phe Phe Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile 
    1250                1255                1260                
Phe Asn Pro Pro Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His 
1265                1270                1275                1280
Tyr Ser Ile Arg Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu 
                1285                1290                1295    
Asn Ser Cys Ser Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp 
            1300                1305                1310        
Ala Gln Ile Thr Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp 
        1315                1320                1325            
Ser Pro Ser Lys Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp 
    1330                1335                1340                
Arg Pro Gln Val Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln 
1345                1350                1355                1360
Lys Thr Met Lys Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu 
                1365                1370                1375    
Leu Thr Ser Met Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp 
            1380                1385                1390        
Gly His Gln Trp Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe 
        1395                1400                1405            
Gln Gly Asn Gln Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro 
    1410                1415                1420                
Pro Leu Leu Thr Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His 
1425                1430                1435                1440
Gln Ile Ala Leu Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu 
                1445                1450                1455    
Tyr 
    

<210> 4
<211> 1463
<212> PRT
<213> Artificial Sequence


<220> 
<221> SOURCE
<222> 1..10
<223> Afstyla - human FVIII B-domain deleted single chain

<220> 
<221> SIGNAL
<222> 1..19
<223> signal sequence

<400> 4
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 Thr 
    770                 775                 780                 
Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser 
785                 790                 795                 800 
Val Glu Met Lys Lys Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn 
                805                 810                 815     
Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala 
            820                 825                 830         
Ala Val Glu Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val 
        835                 840                 845             
Leu Arg Asn Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val 
    850                 855                 860                 
Val Phe Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg 
865                 870                 875                 880 
Gly Glu Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala 
                885                 890                 895     
Glu Val Glu Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg 
            900                 905                 910         
Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg 
        915                 920                 925             
Gln Gly Ala Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys 
    930                 935                 940                 
Thr Tyr Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu 
945                 950                 955                 960 
Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys 
                965                 970                 975     
Asp Val His Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn 
            980                 985                 990         
Thr Leu Asn Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala 
        995                 1000                1005            
Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys Ser Trp Tyr Phe Thr Glu 
    1010                1015                1020                
Asn Met Glu Arg Asn Cys Arg Ala Pro Cys Asn Ile Gln Met Glu Asp 
1025                1030                1035                1040
Pro Thr Phe Lys Glu Asn Tyr Arg Phe His Ala Ile Asn Gly Tyr Ile 
                1045                1050                1055    
Met Asp Thr Leu Pro Gly Leu Val Met Ala Gln Asp Gln Arg Ile Arg 
            1060                1065                1070        
Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu Asn Ile His Ser Ile His 
        1075                1080                1085            
Phe Ser Gly His Val Phe Thr Val Arg Lys Lys Glu Glu Tyr Lys Met 
    1090                1095                1100                
Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe Glu Thr Val Glu Met Leu 
1105                1110                1115                1120
Pro Ser Lys Ala Gly Ile Trp Arg Val Glu Cys Leu Ile Gly Glu His 
                1125                1130                1135    
Leu His Ala Gly Met Ser Thr Leu Phe Leu Val Tyr Ser Asn Lys Cys 
            1140                1145                1150        
Gln Thr Pro Leu Gly Met Ala Ser Gly His Ile Arg Asp Phe Gln Ile 
        1155                1160                1165            
Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala Pro Lys Leu Ala Arg Leu 
    1170                1175                1180                
His Tyr Ser Gly Ser Ile Asn Ala Trp Ser Thr Lys Glu Pro Phe Ser 
1185                1190                1195                1200
Trp Ile Lys Val Asp Leu Leu Ala Pro Met Ile Ile His Gly Ile Lys 
                1205                1210                1215    
Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser Leu Tyr Ile Ser Gln Phe 
            1220                1225                1230        
Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys Trp Gln Thr Tyr Arg Gly 
        1235                1240                1245            
Asn Ser Thr Gly Thr Leu Met Val Phe Phe Gly Asn Val Asp Ser Ser 
    1250                1255                1260                
Gly Ile Lys His Asn Ile Phe Asn Pro Pro Ile Ile Ala Arg Tyr Ile 
1265                1270                1275                1280
Arg Leu His Pro Thr His Tyr Ser Ile Arg Ser Thr Leu Arg Met Glu 
                1285                1290                1295    
Leu Met Gly Cys Asp Leu Asn Ser Cys Ser Met Pro Leu Gly Met Glu 
            1300                1305                1310        
Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr Ala Ser Ser Tyr Phe Thr 
        1315                1320                1325            
Asn Met Phe Ala Thr Trp Ser Pro Ser Lys Ala Arg Leu His Leu Gln 
    1330                1335                1340                
Gly Arg Ser Asn Ala Trp Arg Pro Gln Val Asn Asn Pro Lys Glu Trp 
1345                1350                1355                1360
Leu Gln Val Asp Phe Gln Lys Thr Met Lys Val Thr Gly Val Thr Thr 
                1365                1370                1375    
Gln Gly Val Lys Ser Leu Leu Thr Ser Met Tyr Val Lys Glu Phe Leu 
            1380                1385                1390        
Ile Ser Ser Ser Gln Asp Gly His Gln Trp Thr Leu Phe Phe Gln Asn 
        1395                1400                1405            
Gly Lys Val Lys Val Phe Gln Gly Asn Gln Asp Ser Phe Thr Pro Val 
    1410                1415                1420                
Val Asn Ser Leu Asp Pro Pro Leu Leu Thr Arg Tyr Leu Arg Ile His 
1425                1430                1435                1440
Pro Gln Ser Trp Val His Gln Ile Ala Leu Arg Met Glu Val Leu Gly 
                1445                1450                1455    
Cys Glu Ala Gln Asp Leu Tyr 
            1460            

<210> 5
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-19M

<220> 
<221> DOMAIN
<222> 20..348
<223> A1

<220> 
<221> MUTAGEN
<222> 79
<223> N79S

<220> 
<221> MUTAGEN
<222> 112
<223> S112T

<220> 
<221> MUTAGEN
<222> 160
<223> L160S

<220> 
<221> MUTAGEN
<222> 171
<223> L171Q

<220> 
<221> MUTAGEN
<222> 184
<223> V184A

<220> 
<221> MUTAGEN
<222> 223
<223> N233D

<220> 
<221> MUTAGEN
<222> 265
<223> I265T

<220> 
<221> MUTAGEN
<222> 299
<223> N299D

<220> 
<221> DOMAIN
<222> 349..398
<223> a1

<220> 
<221> DOMAIN
<222> 399..730
<223> A2

<220> 
<221> MUTAGEN
<222> 426
<223> Y426H

<220> 
<221> MUTAGEN
<222> 507
<223> S507E

<220> 
<221> MUTAGEN
<222> 555
<223> F555H

<220> 
<221> MUTAGEN
<222> 616
<223> N616E

<220> 
<221> MUTAGEN
<222> 706
<223> L706N

<220> 
<221> DOMAIN
<222> 731..759
<223> a2

<220> 
<221> MUTAGEN
<222> 748
<223> Y748S

<220> 
<221> DOMAIN
<222> 760..849
<223> truncated B-domain

<220> 
<221> DOMAIN
<222> 850..894
<223> a3

<220> 
<221> DOMAIN
<222> 895..1221
<223> A3

<220> 
<221> MUTAGEN
<222> 1019
<223> K1837E

<220> 
<221> MUTAGEN
<222> 1220
<223> N2038D

<220> 
<221> DOMAIN
<222> 1222..1374
<223> C1

<220> 
<221> MUTAGEN
<222> 1259
<223> S2077G

<220> 
<221> DOMAIN
<222> 1375..1533
<223> C2

<220> 
<221> MUTAGEN
<222> 1497
<223> S2315T

<220> 
<221> MUTAGEN
<222> 1515
<223> V2333A

<400> 5
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 Ser 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 Thr 
            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 Ser 
145                 150                 155                 160 
Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Gln Cys Leu Thr Tyr Ser 
                165                 170                 175     
Tyr Leu Ser His Val Asp Leu Ala 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 Asp 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 Thr 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 Asp 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 His 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 Glu 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 His 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 Glu 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 Asn 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Glu Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asp Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Gly Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Thr Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Ala His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 6
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-18M

<400> 6
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 Ser 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 Thr 
            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 Ser 
145                 150                 155                 160 
Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Gln Cys Leu Thr Tyr Ser 
                165                 170                 175     
Tyr Leu Ser His Val Asp Leu Ala 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 Asp 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 Thr 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 Asp 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 His 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 Glu 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 His 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 Glu 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 Asn 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asp Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Gly Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Thr Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Ala His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 7
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-15M

<400> 7
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 Ser 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 Thr 
            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 Ser 
145                 150                 155                 160 
Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Gln Cys Leu Thr Tyr Ser 
                165                 170                 175     
Tyr Leu Ser His Val Asp Leu Ala 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 Asp 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 Thr 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 Asp 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 His 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 Glu 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 His 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 Glu 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 Asn 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Glu Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 8
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-A1-7M

<400> 8
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 Ser 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 Thr 
            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 Ser 
145                 150                 155                 160 
Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Gln Cys Leu Thr Tyr Ser 
                165                 170                 175     
Tyr Leu Ser His Val Asp Leu Ala 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 Asp 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 Thr 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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 9
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-A2-4M

<400> 9
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 His 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 Glu 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 Asn 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 10
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-BA3-1M

<400> 10
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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Glu Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 11
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-A3C2-4M

<400> 11
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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asp Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Gly Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Thr Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Ala His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 12
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-GOF1

<400> 12
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 Gln 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 Glu 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Ala His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 13
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-GOF2

<400> 13
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 Gln 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 Asp 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 Glu 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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Ala His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 14
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-LS1

<400> 14
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 Thr 
            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 Glu 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 Ser Leu Leu Ser Lys 
            740                 745                 750         
Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Glu Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asp Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 15
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-LS2

<220> 
<221> MUTAGEN
<222> 112
<223> S112T

<220> 
<221> MUTAGEN
<222> 426
<223> Y426H

<220> 
<221> MUTAGEN
<222> 754
<223> N754D

<220> 
<221> MUTAGEN
<222> 1019
<223> K1837E

<220> 
<221> MUTAGEN
<222> 1220
<223> N2038D

<400> 15
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 Thr 
            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 His 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 Asp Ala Ile Glu Pro Arg Ser Phe Ser Gln Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Glu Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asp Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 16
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 16
Asp His Leu Phe Asn Ile Ala Lys Pro Arg Pro Pro Trp Met Gly 
1               5                   10                  15  

<210> 17
<211> 18
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 17
Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
1               5                   10                  15      
Ser Leu 
        

<210> 18
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 18
Val Trp Gln Val Leu Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu 
1               5                   10                  15      



<210> 19
<211> 18
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 19
Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser His Val Asp Leu 
1               5                   10                  15      
Val Lys 
        

<210> 20
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 20
His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
1               5                   10                  15      



<210> 21
<211> 18
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 21
Thr Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu 
1               5                   10                  15      
Gly Lys 
        

<210> 22
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 22
Gly Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp 
1               5                   10                  15  

<210> 23
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 23
Met His Thr Val Asn Gly Tyr Val Asn Arg Ser Leu Pro Gly Leu Ile 
1               5                   10                  15      
Gly 
    

<210> 24
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 24
Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
1               5                   10                  15      
Ser 
    

<210> 25
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 25
Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu 
1               5                   10                  15      
Gly 
    

<210> 26
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 26
Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro Gln Arg Ile 
1               5                   10                  15      
Gly Arg Lys 
            

<210> 27
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 27
Gly Asp Thr Leu Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr 
1               5                   10                  15      
Asn Ile Tyr 
            

<210> 28
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 28
Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val 
1               5                   10                  15      
Lys His Leu 
            

<210> 29
<211> 22
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 29
Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
1               5                   10                  15      
Asp Leu Ala Ser Gly Leu 
            20          

<210> 30
<211> 18
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 30
Thr Glu Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu 
1               5                   10                  15      
Glu Asp 
        

<210> 31
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 31
Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
1               5                   10                  15      
Phe Asp Ser 
            

<210> 32
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 32
Glu Val Ala Tyr Trp Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe 
1               5                   10                  15      
Leu 
    

<210> 33
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 33
Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp Ile Leu 
1               5                   10                  15  

<210> 34
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 34
Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala Ile Glu Pro Arg Ser 
1               5                   10                  15      



<210> 35
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 35
Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala 
1               5                   10                  15  

<210> 36
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 36
Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
1               5                   10                  15      



<210> 37
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 37
Lys Thr Tyr Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp 
1               5                   10                  15      



<210> 38
<211> 21
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 38
Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His Ala Ile Asn Gly Tyr 
1               5                   10                  15      
Ile Met Asp Thr Leu 
            20      

<210> 39
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 39
Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu Asn 
1               5                   10                  15      
Ile His Ser 
            

<210> 40
<211> 16
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 40
Met Ser Thr Leu Phe Leu Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu 
1               5                   10                  15      



<210> 41
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 41
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
1               5                   10                  15      
Thr Lys Glu 
            

<210> 42
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 42
Ser Ser Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly 
1               5                   10                  15      
Lys Lys Trp 
            

<210> 43
<211> 18
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 43
Gly Lys Lys Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met 
1               5                   10                  15      
Val Phe 
        

<210> 44
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 44
Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg Ser 
1               5                   10                  15      
Thr 
    

<210> 45
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 45
Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
1               5                   10                  15  

<210> 46
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 46
Lys Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln 
1               5                   10                  15      
Val 
    

<210> 47
<211> 17
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 47
Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys Val Thr Gly Val Thr 
1               5                   10                  15      
Thr 
    

<210> 48
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 48
Thr Ser Met Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly 
1               5                   10                  15      
His Gln Trp 
            

<210> 49
<211> 19
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 49
Gln Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu 
1               5                   10                  15      
Thr Arg Tyr 
            

<210> 50
<211> 15
<212> PRT
<213> Homo sapiens


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 50
Pro Gln Ser Trp Val His Gln Ile Ala Leu Arg Met Glu Val Leu 
1               5                   10                  15  

<210> 51
<211> 1533
<212> PRT
<213> Artificial Sequence


<220> 
<221> SIGNAL
<222> 1..19

<220> 
<223> FVIII-A1A2-3M

<400> 51
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 Asp 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 His 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 Glu 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 Asp Pro Leu Ala Trp 
        755                 760                 765             
Asp Asn His Tyr Gly Thr Gln Ile Pro Lys Glu Glu Trp Lys Ser Gln 
    770                 775                 780                 
Glu Lys Ser Pro Glu Lys Thr Ala Phe Lys Lys Lys Asp Thr Ile Leu 
785                 790                 795                 800 
Ser Leu Asn Ala Cys Glu Ser Asn His Ala Ile Ala Ala Ile Asn Glu 
                805                 810                 815     
Gly Gln Asn Lys Pro Glu Ile Glu Val Thr Trp Ala Lys Gln Gly Arg 
            820                 825                 830         
Thr Glu Arg Leu Cys Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
        835                 840                 845             
Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp 
    850                 855                 860                 
Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile 
865                 870                 875                 880 
Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr 
                885                 890                 895     
Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met 
            900                 905                 910         
Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val 
        915                 920                 925             
Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe 
    930                 935                 940                 
Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu 
945                 950                 955                 960 
Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe 
                965                 970                 975     
Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser 
            980                 985                 990         
Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val 
        995                 1000                1005            
Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met 
    1010                1015                1020                
Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser 
1025                1030                1035                1040
Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu 
                1045                1050                1055    
Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val 
            1060                1065                1070        
Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr Lys 
        1075                1080                1085            
Ser Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys 
    1090                1095                1100                
Asn Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His 
1105                1110                1115                1120
Ala Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala 
                1125                1130                1135    
Gln Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu 
            1140                1145                1150        
Asn Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys 
        1155                1160                1165            
Lys Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe 
    1170                1175                1180                
Glu Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu 
1185                1190                1195                1200
Cys Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu 
                1205                1210                1215    
Val Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His 
            1220                1225                1230        
Ile Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala 
        1235                1240                1245            
Pro Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser 
    1250                1255                1260                
Thr Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met 
1265                1270                1275                1280
Ile Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser 
                1285                1290                1295    
Leu Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys 
            1300                1305                1310        
Trp Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe 
        1315                1320                1325            
Gly Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro 
    1330                1335                1340                
Ile Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg 
1345                1350                1355                1360
Ser Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser 
                1365                1370                1375    
Met Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr 
            1380                1385                1390        
Ala Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys 
        1395                1400                1405            
Ala Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val 
    1410                1415                1420                
Asn Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys 
1425                1430                1435                1440
Val Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met 
                1445                1450                1455    
Tyr Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp 
            1460                1465                1470        
Thr Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln 
        1475                1480                1485            
Asp Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr 
    1490                1495                1500                
Arg Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu 
1505                1510                1515                1520
Arg Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
                1525                1530            

<210> 52
<211> 4605
<212> DNA
<213> Artificial Sequence


<220> 
<223> FVIII-19M na

<400> 52
atgcagatcg agctgtctac ctgcttcttc ctgtgcctgc tgcggttctg cttcagcgcc       60

acccggcggt actacctggg cgccgtggaa ctgagctggg actacatgca gagcgacctg      120

ggcgagctgc ccgtggacgc cagattcccc ccaagagtgc ccaagagctt ccccttcaac      180

acctccgtgg tgtacaagaa aaccctgttc gtcgagttca ccgaccacct gttctccatc      240

gccaagccca gacccccctg gatgggcctg ctgggcccta caatccaggc cgaggtgtac      300

gacaccgtgg tcatcaccct gaagaacatg gccacccacc ccgtgtccct gcacgccgtg      360

ggcgtgtcct actggaaggc cagcgagggc gccgagtacg acgaccagac cagccagcgc      420

gagaaagagg acgacaaagt ctttcctggc ggcagccata cctacgtgtg gcaggtctcc      480

aaagaaaacg gccccatggc ctccgacccc cagtgcctga cctacagcta cctgagccac      540

gtggacctgg ccaaggacct gaacagcggc ctgatcggcg ccctgctcgt gtgcagagag      600

ggcagcctgg ccaaagagaa aacccagacc ctgcacaagt tcatcctgct gttcgccgtg      660

ttcgacgagg gcaagagctg gcacagcgag acaaaggaca gcctgatgca ggaccgggac      720

gccgcctctg ccagagcctg gcctaagatg cacaccgtga acggctacgt gaacagaagc      780

ctgcccggac tgaccggctg ccaccggaag tccgtgtact ggcacgtgat cggcatgggt      840

accacccccg aggtgcacag catctttctg gaaggacaca ccttcctcgt gcgggaccac      900

cggcaggcca gcctggaaat cagccctatc accttcctga ccgcccagac actgctgatg      960

gacctgggcc agttcctgct gttttgccac atcagcagcc accagcacga cggcatggaa     1020

gcctacgtga aggtggacag ctgccccgag gaaccccagc tgcggatgaa gaacaacgag     1080

gaagccgagg actacgacga cgacctgacc gacagcgaga tggacgtcgt cagattcgat     1140

gacgacaaca gccccagctt catccagatc agaagcgtgg ccaagaagca ccccaagacc     1200

tgggtgcact atatcgccgc cgaggaagag gactgggact acgcccctct ggtgctggcc     1260

cccgacgaca gaagccacaa gagccagtac ctgaacaatg gcccccagcg gatcggccgg     1320

aagtacaaga aagtgcggtt catggcctac accgacgaga cattcaagac cagagaggcc     1380

atccagcacg agagcggcat cctgggcccc ctgctgtacg gcgaagtggg cgacaccctg     1440

ctgattatct tcaagaacca ggccagccgg ccctacaaca tctaccccca cggcatcacc     1500

gacgtgcggc ccctgtacga gagacggctg cccaagggcg tgaagcacct gaaggacttc     1560

cccatcctgc ccggggagat cttcaagtac aagtggaccg tgaccgtgga agatggcccc     1620

accaagagcg accccagatg cctgacccgg tactacagca gccacgtgaa catggaacgg     1680

gacctggcct ccgggctgat cggccctctg ctgatctgct acaaagaaag cgtggaccag     1740

cggggcaacc agatcatgag cgacaagcgg aacgtgatcc tgttcagcgt gttcgatgag     1800

aacagaagct ggtatctgac cgagaatatc cagcggttcc tgcccgagcc tgccggcgtg     1860

cagctggaag atcccgagtt ccaggccagc aacatcatgc actccatcaa tggctacgtg     1920

ttcgacagcc tgcagctgag cgtgtgcctg cacgaggtgg cctactggta catcctgagc     1980

atcggcgccc agaccgactt cctgagcgtg ttcttcagcg gctacacctt caagcacaag     2040

atggtgtacg aggataccct gaccctgttc cccttctccg gcgaaaccgt gttcatgagc     2100

atggaaaacc ccggcaactg gattctgggc tgccacaaca gcgacttccg gaaccggggc     2160

atgaccgccc tgctgaaggt gtccagctgc gacaagaaca ccggcgacta ctacgaggac     2220

agctacgagg atatcagcgc cagcctgctg agcaagaaca acgccatcga gcctcggagc     2280

ttctcccagg atcctctggc ctgggacaac cactacggca cccagatccc caaagaggaa     2340

tggaagtccc aggaaaagag ccccgagaaa accgccttca agaagaagga caccatcctg     2400

agcctgaacg cctgcgagag caaccacgcc attgccgcca tcaacgaggg ccagaacaag     2460

cccgagatcg aagtgacctg ggctaagcag ggccggaccg agagactgtg cagccagaac     2520

ccccccgtgc tgaagcggca ccagagagag atcacccgga ccaccctgca gagcgaccag     2580

gaagagatcg actacgacga caccatcagc gtcgagatga agaaagagga cttcgacatc     2640

tacgacgagg acgagaacca gagcccccgg tccttccaga agaaaacccg gcactacttt     2700

atcgccgccg tggaacggct gtgggactac ggcatgagca gcagccccca cgtgctgcgg     2760

aatagagccc agagcggcag cgtgccccag ttcaagaaag tggtgttcca ggagttcacc     2820

gacggcagct tcacccagcc tctgtaccgg ggcgagctga acgagcacct gggcctgctg     2880

ggcccctaca tccgggccga ggtggaagat aacatcatgg tcaccttccg gaaccaggcc     2940

agccggccct acagcttcta cagcagcctg atctcctacg aagaggacca gcggcagggc     3000

gccgagcccc ggaagaactt cgtgaagccc aacgagacaa agacctactt ctgggaggtg     3060

cagcaccaca tggcccccac caaggacgaa ttcgactgca aggcctgggc ctacttcagc     3120

gacgtggacc tggaaaagga cgtgcacagc ggcctgatcg gccccctgct cgtgtgccac     3180

accaacaccc tgaaccccgc ccacggccgg caggtcacag tgcaggaatt tgccctgttc     3240

ttcaccatct tcgacgagac taagagctgg tacttcaccg agaacatgga acggaactgc     3300

agagccccct gcaacatcca gatggaagat cccaccttca aagagaacta ccggttccac     3360

gccatcaatg gctacatcat ggacaccctg cccggcctgg tcatggccca ggaccagaga     3420

atccggtggt atctgctgag catgggcagc aacgagaaca tccacagcat ccacttcagc     3480

ggccacgtgt tcaccgtgcg gaagaaagaa gagtacaaga tggccctgta caacctgtac     3540

cccggcgtgt tcgagacagt ggaaatgctg cccagcaagg ccggcatctg gcgggtggaa     3600

tgtctgatcg gcgagcatct gcacgccggc atgtccaccc tgtttctggt gtacagcgac     3660

aagtgccaga cccccctggg catggccagc ggccacatcc gggatttcca gatcaccgcc     3720

tccggccagt acggccagtg ggcccctaaa ctggcccggc tgcactacag cggcggcatc     3780

aacgcctggt ccaccaaaga gcccttcagc tggatcaagg tggacctgct ggcccccatg     3840

attatccacg gcatcaagac acagggcgcc agacagaagt tcagcagcct gtacatcagc     3900

cagttcatca tcatgtacag cctggatggc aagaagtggc agacctaccg gggcaacagc     3960

accggcaccc tgatggtgtt cttcggcaac gtggacagca gcggcatcaa gcacaacatc     4020

ttcaaccccc ccatcattgc ccggtacatc cggctgcacc ccacccacta cagcatccgg     4080

tccaccctgc ggatggaact gatgggctgc gacctgaaca gctgctccat gcctctgggc     4140

atggaaagca aggccatcag cgacgcccag atcacagcca gcagctactt caccaacatg     4200

ttcgccacct ggtccccatc caaggccaga ctgcatctgc agggcagaag caatgcctgg     4260

cggcctcagg tcaacaaccc caaagaatgg ctccaggtgg acttccagaa aaccatgaag     4320

gtcacaggcg tgaccaccca gggcgtgaag tccctgctga cctctatgta cgtgaaagag     4380

ttcctgatct ccagcagcca ggacggccac cagtggaccc tgttctttca gaacggcaaa     4440

gtgaaagtgt tccagggcaa ccaggactcc ttcacccccg tggtcaacac cctggacccc     4500

ccactgctga ccagatacct gagaatccac ccccagagct gggcccacca gatcgccctg     4560

agaatggaag tgctgggatg cgaggcccag gatctgtact gatag                     4605


<210> 53
<211> 4605
<212> DNA
<213> Artificial Sequence


<220> 
<223> FVIII-6rs na

<400> 53
atgcagatcg agctgtctac ctgcttcttc ctgtgcctgc tgcggttctg cttcagcgcc       60

acccggcggt actacctggg cgccgtggaa ctgagctggg actacatgca gagcgacctg      120

ggcgagctgc ccgtggacgc cagattcccc ccaagagtgc ccaagagctt ccccttcaac      180

acctccgtgg tgtacaagaa aaccctgttc gtcgagttca ccgaccacct gttcaatatc      240

gccaagccca gacccccctg gatgggcctg ctgggcccta caatccaggc cgaggtgtac      300

gacaccgtgg tcatcaccct gaagaacatg gccagccacc ccgtgtccct gcacgccgtg      360

ggcgtgtcct actggaaggc cagcgagggc gccgagtacg acgaccagac cagccagcgc      420

gagaaagagg acgacaaagt ctttcctggc ggcagccata cctacgtgtg gcaggtcctg      480

aaagaaaacg gccccatggc ctccgacccc ctgtgcctga cctacagcta cctgagccac      540

gtggacctgg tcaaggacct gaacagcggc ctgatcggcg ccctgctcgt gtgcagagag      600

ggcagcctgg ccaaagagaa aacccagacc ctgcacaagt tcatcctgct gttcgccgtg      660

ttcgacgagg gcaagagctg gcacagcgag acaaagaaca gcctgatgca ggaccgggac      720

gccgcctctg ccagagcctg gcctaagatg cacaccgtga acggctacgt gaacagaagc      780

ctgcccggac tgatcggctg ccaccggaag tccgtgtact ggcacgtgat cggcatgggt      840

accacccccg aggtgcacag catctttctg gaaggacaca ccttcctcgt gcggaaccac      900

cggcaggcca gcctggaaat cagccctatc accttcctga ccgcccagac actgctgatg      960

gacctgggcc agttcctgct gttttgccac atcagcagcc accagcacga cggcatggaa     1020

gcctacgtga aggtggacag ctgccccgag gaaccccagc tgcggatgaa gaacaacgag     1080

gaagccgagg actacgacga cgacctgacc gacagcgaga tggacgtcgt cagattcgat     1140

gacgacaaca gccccagctt catccagatc agaagcgtgg ccaagaagca ccccaagacc     1200

tgggtgcact atatcgccgc cgaggaagag gactgggact acgcccctct ggtgctggcc     1260

cccgacgaca gaagctacaa gagccagtac ctgaacaatg gcccccagcg gatcggccgg     1320

aagtacaaga aagtgcggtt catggcctac accgacgaga cattcaagac cagagaggcc     1380

atccagcacg agagcggcat cctgggcccc ctgctgtacg gcgaagtggg cgacaccctg     1440

ctgattatct tcaagaacca ggccagccgg ccctacaaca tctaccccca cggcatcacc     1500

gacgtgcggc ccctgtacag cagacggctg cccaagggcg tgaagcacct gaaggacttc     1560

cccatcctgc ccggggagat cttcaagtac aagtggaccg tgaccgtgga agatggcccc     1620

accaagagcg accccagatg cctgacccgg tactacagca gcttcgtgaa catggaacgg     1680

gacctggcct ccgggctgat cggccctctg ctgatctgct acaaagaaag cgtggaccag     1740

cggggcaacc agatcatgag cgacaagcgg aacgtgatcc tgttcagcgt gttcgatgag     1800

aacagaagct ggtatctgac cgagaatatc cagcggttcc tgcccaaccc tgccggcgtg     1860

cagctggaag atcccgagtt ccaggccagc aacatcatgc actccatcaa tggctacgtg     1920

ttcgacagcc tgcagctgag cgtgtgcctg cacgaggtgg cctactggta catcctgagc     1980

atcggcgccc agaccgactt cctgagcgtg ttcttcagcg gctacacctt caagcacaag     2040

atggtgtacg aggataccct gaccctgttc cccttctccg gcgaaaccgt gttcatgagc     2100

atggaaaacc ccggcctgtg gattctgggc tgccacaaca gcgacttccg gaaccggggc     2160

atgaccgccc tgctgaaggt gtccagctgc gacaagaaca ccggcgacta ctacgaggac     2220

agctacgagg atatcagcgc ctacctgctg agcaagaaca acgccatcga gcctcggagc     2280

ttctcccagg atcctctggc ctgggacaac cactacggca cccagatccc caaagaggaa     2340

tggaagtccc aggaaaagag ccccgagaaa accgccttca agaagaagga caccatcctg     2400

agcctgaacg cctgcgagag caaccacgcc attgccgcca tcaacgaggg ccagaacaag     2460

cccgagatcg aagtgacctg ggctaagcag ggccggaccg agagactgtg cagccagaac     2520

ccccccgtgc tgaagcggca ccagagagag atcacccgga ccaccctgca gagcgaccag     2580

gaagagatcg actacgacga caccatcagc gtcgagatga agaaagagga cttcgacatc     2640

tacgacgagg acgagaacca gagcccccgg tccttccaga agaaaacccg gcactacttt     2700

atcgccgccg tggaacggct gtgggactac ggcatgagca gcagccccca cgtgctgcgg     2760

aatagagccc agagcggcag cgtgccccag ttcaagaaag tggtgttcca ggagttcacc     2820

gacggcagct tcacccagcc tctgtaccgg ggcgagctga acgagcacct gggcctgctg     2880

ggcccctaca tccgggccga ggtggaagat aacatcatgg tcaccttccg gaaccaggcc     2940

agccggccct acagcttcta cagcagcctg atctcctacg aagaggacca gcggcagggc     3000

gccgagcccc ggaagaactt cgtgaagccc aacgagacaa agacctactt ctggaaggtg     3060

cagcaccaca tggcccccac caaggacgaa ttcgactgca aggcctgggc ctacttcagc     3120

gacgtggacc tggaaaagga cgtgcacagc ggcctgatcg gccccctgct cgtgtgccac     3180

accaacaccc tgaaccccgc ccacggccgg caggtcacag tgcaggaatt tgccctgttc     3240

ttcaccatct tcgacgagac taagagctgg tacttcaccg agaacatgga acggaactgc     3300

agagccccct gcaacatcca gatggaagat cccaccttca aagagaacta ccggttccac     3360

gccatcaatg gctacatcat ggacaccctg cccggcctgg tcatggccca ggaccagaga     3420

atccggtggt atctgctgag catgggcagc aacgagaaca tccacagcat ccacttcagc     3480

ggccacgtgt tcaccgtgcg gaagaaagaa gagtacaaga tggccctgta caacctgtac     3540

cccggcgtgt tcgagacagt ggaaatgctg cccagcaagg ccggcatctg gcgggtggaa     3600

tgtctgatcg gcgagcatct gcacgccggc atgtccaccc tgtttctggt gtacagcaac     3660

aagtgccaga cccccctggg catggccagc ggccacatcc gggatttcca gatcaccgcc     3720

tccggccagt acggccagtg ggcccctaaa ctggcccggc tgcactacag cggcagcatc     3780

aacgcctggt ccaccaaaga gcccttcagc tggatcaagg tggacctgct ggcccccatg     3840

attatccacg gcatcaagac acagggcgcc agacagaagt tcagcagcct gtacatcagc     3900

cagttcatca tcatgtacag cctggatggc aagaagtggc agacctaccg gggcaacagc     3960

accggcaccc tgatggtgtt cttcggcaac gtggacagca gcggcatcaa gcacaacatc     4020

ttcaaccccc ccatcattgc ccggtacatc cggctgcacc ccacccacta cagcatccgg     4080

tccaccctgc ggatggaact gatgggctgc gacctgaaca gctgctccat gcctctgggc     4140

atggaaagca aggccatcag cgacgcccag atcacagcca gcagctactt caccaacatg     4200

ttcgccacct ggtccccatc caaggccaga ctgcatctgc agggcagaag caatgcctgg     4260

cggcctcagg tcaacaaccc caaagaatgg ctccaggtgg acttccagaa aaccatgaag     4320

gtcacaggcg tgaccaccca gggcgtgaag tccctgctga cctctatgta cgtgaaagag     4380

ttcctgatct ccagcagcca ggacggccac cagtggaccc tgttctttca gaacggcaaa     4440

gtgaaagtgt tccagggcaa ccaggactcc ttcacccccg tggtcaactc cctggacccc     4500

ccactgctga ccagatacct gagaatccac ccccagagct gggtgcacca gatcgccctg     4560

agaatggaag tgctgggatg cgaggcccag gatctgtact gatag                     4605


<210> 54
<211> 16
<212> PRT
<213> Artificial Sequence


<220> 
<223> Immunogenic cluster identified in FVIII

<400> 54
Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu Val Tyr Ser 
1               5                   10                  15      



