                         SEQUENCE LISTING

<110>  Pfizer Inc.
 
<120>  IMPROVED MUTEINS OF CLOTTING FACTOR VIII

<130>  PC72098A

<150>  61/948,186
<151>  2014-03-05

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  2332
<212>  PRT
<213>  Homo sapiens

<400>  1

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile Ala Lys Pro 
    50                  55                  60                  


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


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


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp Ala Ala Ser 
    210                 215                 220                 


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
        275                 280                 285             


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro Ser Thr Arg 
            740                 745                 750         


Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp Ile Glu Lys 
        755                 760                 765             


Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys Ile Gln Asn 
    770                 775                 780                 


Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser Pro Thr Pro 
785                 790                 795                 800 


His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr Glu Thr Phe 
                805                 810                 815     


Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn Ser Leu Ser 
            820                 825                 830         


Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly Asp Met Val 
        835                 840                 845             


Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu Lys Leu Gly 
    850                 855                 860                 


Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys Val Ser Ser 
865                 870                 875                 880 


Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn Leu Ala Ala 
                885                 890                 895     


Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met Pro Val His 
            900                 905                 910         


Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys Ser Ser Pro 
        915                 920                 925             


Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu Asn Asn Asp 
    930                 935                 940                 


Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu Ser Ser Trp 
945                 950                 955                 960 


Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe Lys Gly Lys 
                965                 970                 975     


Arg Ala His Gly Pro Ala Leu Leu Thr Lys Asp Asn Ala Leu Phe Lys 
            980                 985                 990         


Val Ser Ile Ser Leu Leu Lys Thr  Asn Lys Thr Ser Asn  Asn Ser Ala 
        995                 1000                 1005             


Thr Asn  Arg Lys Thr His Ile  Asp Gly Pro Ser Leu  Leu Ile Glu 
    1010                 1015                 1020             


Asn Ser  Pro Ser Val Trp Gln  Asn Ile Leu Glu Ser  Asp Thr Glu 
    1025                 1030                 1035             


Phe Lys  Lys Val Thr Pro Leu  Ile His Asp Arg Met  Leu Met Asp 
    1040                 1045                 1050             


Lys Asn  Ala Thr Ala Leu Arg  Leu Asn His Met Ser  Asn Lys Thr 
    1055                 1060                 1065             


Thr Ser  Ser Lys Asn Met Glu  Met Val Gln Gln Lys  Lys Glu Gly 
    1070                 1075                 1080             


Pro Ile  Pro Pro Asp Ala Gln  Asn Pro Asp Met Ser  Phe Phe Lys 
    1085                 1090                 1095             


Met Leu  Phe Leu Pro Glu Ser  Ala Arg Trp Ile Gln  Arg Thr His 
    1100                 1105                 1110             


Gly Lys  Asn Ser Leu Asn Ser  Gly Gln Gly Pro Ser  Pro Lys Gln 
    1115                 1120                 1125             


Leu Val  Ser Leu Gly Pro Glu  Lys Ser Val Glu Gly  Gln Asn Phe 
    1130                 1135                 1140             


Leu Ser  Glu Lys Asn Lys Val  Val Val Gly Lys Gly  Glu Phe Thr 
    1145                 1150                 1155             


Lys Asp  Val Gly Leu Lys Glu  Met Val Phe Pro Ser  Ser Arg Asn 
    1160                 1165                 1170             


Leu Phe  Leu Thr Asn Leu Asp  Asn Leu His Glu Asn  Asn Thr His 
    1175                 1180                 1185             


Asn Gln  Glu Lys Lys Ile Gln  Glu Glu Ile Glu Lys  Lys Glu Thr 
    1190                 1195                 1200             


Leu Ile  Gln Glu Asn Val Val  Leu Pro Gln Ile His  Thr Val Thr 
    1205                 1210                 1215             


Gly Thr  Lys Asn Phe Met Lys  Asn Leu Phe Leu Leu  Ser Thr Arg 
    1220                 1225                 1230             


Gln Asn  Val Glu Gly Ser Tyr  Asp Gly Ala Tyr Ala  Pro Val Leu 
    1235                 1240                 1245             


Gln Asp  Phe Arg Ser Leu Asn  Asp Ser Thr Asn Arg  Thr Lys Lys 
    1250                 1255                 1260             


His Thr  Ala His Phe Ser Lys  Lys Gly Glu Glu Glu  Asn Leu Glu 
    1265                 1270                 1275             


Gly Leu  Gly Asn Gln Thr Lys  Gln Ile Val Glu Lys  Tyr Ala Cys 
    1280                 1285                 1290             


Thr Thr  Arg Ile Ser Pro Asn  Thr Ser Gln Gln Asn  Phe Val Thr 
    1295                 1300                 1305             


Gln Arg  Ser Lys Arg Ala Leu  Lys Gln Phe Arg Leu  Pro Leu Glu 
    1310                 1315                 1320             


Glu Thr  Glu Leu Glu Lys Arg  Ile Ile Val Asp Asp  Thr Ser Thr 
    1325                 1330                 1335             


Gln Trp  Ser Lys Asn Met Lys  His Leu Thr Pro Ser  Thr Leu Thr 
    1340                 1345                 1350             


Gln Ile  Asp Tyr Asn Glu Lys  Glu Lys Gly Ala Ile  Thr Gln Ser 
    1355                 1360                 1365             


Pro Leu  Ser Asp Cys Leu Thr  Arg Ser His Ser Ile  Pro Gln Ala 
    1370                 1375                 1380             


Asn Arg  Ser Pro Leu Pro Ile  Ala Lys Val Ser Ser  Phe Pro Ser 
    1385                 1390                 1395             


Ile Arg  Pro Ile Tyr Leu Thr  Arg Val Leu Phe Gln  Asp Asn Ser 
    1400                 1405                 1410             


Ser His  Leu Pro Ala Ala Ser  Tyr Arg Lys Lys Asp  Ser Gly Val 
    1415                 1420                 1425             


Gln Glu  Ser Ser His Phe Leu  Gln Gly Ala Lys Lys  Asn Asn Leu 
    1430                 1435                 1440             


Ser Leu  Ala Ile Leu Thr Leu  Glu Met Thr Gly Asp  Gln Arg Glu 
    1445                 1450                 1455             


Val Gly  Ser Leu Gly Thr Ser  Ala Thr Asn Ser Val  Thr Tyr Lys 
    1460                 1465                 1470             


Lys Val  Glu Asn Thr Val Leu  Pro Lys Pro Asp Leu  Pro Lys Thr 
    1475                 1480                 1485             


Ser Gly  Lys Val Glu Leu Leu  Pro Lys Val His Ile  Tyr Gln Lys 
    1490                 1495                 1500             


Asp Leu  Phe Pro Thr Glu Thr  Ser Asn Gly Ser Pro  Gly His Leu 
    1505                 1510                 1515             


Asp Leu  Val Glu Gly Ser Leu  Leu Gln Gly Thr Glu  Gly Ala Ile 
    1520                 1525                 1530             


Lys Trp  Asn Glu Ala Asn Arg  Pro Gly Lys Val Pro  Phe Leu Arg 
    1535                 1540                 1545             


Val Ala  Thr Glu Ser Ser Ala  Lys Thr Pro Ser Lys  Leu Leu Asp 
    1550                 1555                 1560             


Pro Leu  Ala Trp Asp Asn His  Tyr Gly Thr Gln Ile  Pro Lys Glu 
    1565                 1570                 1575             


Glu Trp  Lys Ser Gln Glu Lys  Ser Pro Glu Lys Thr  Ala Phe Lys 
    1580                 1585                 1590             


Lys Lys  Asp Thr Ile Leu Ser  Leu Asn Ala Cys Glu  Ser Asn His 
    1595                 1600                 1605             


Ala Ile  Ala Ala Ile Asn Glu  Gly Gln Asn Lys Pro  Glu Ile Glu 
    1610                 1615                 1620             


Val Thr  Trp Ala Lys Gln Gly  Arg Thr Glu Arg Leu  Cys Ser Gln 
    1625                 1630                 1635             


Asn Pro  Pro Val Leu Lys Arg  His Gln Arg Glu Ile  Thr Arg Thr 
    1640                 1645                 1650             


Thr Leu  Gln Ser Asp Gln Glu  Glu Ile Asp Tyr Asp  Asp Thr Ile 
    1655                 1660                 1665             


Ser Val  Glu Met Lys Lys Glu  Asp Phe Asp Ile Tyr  Asp Glu Asp 
    1670                 1675                 1680             


Glu Asn  Gln Ser Pro Arg Ser  Phe Gln Lys Lys Thr  Arg His Tyr 
    1685                 1690                 1695             


Phe Ile  Ala Ala Val Glu Arg  Leu Trp Asp Tyr Gly  Met Ser Ser 
    1700                 1705                 1710             


Ser Pro  His Val Leu Arg Asn  Arg Ala Gln Ser Gly  Ser Val Pro 
    1715                 1720                 1725             


Gln Phe  Lys Lys Val Val Phe  Gln Glu Phe Thr Asp  Gly Ser Phe 
    1730                 1735                 1740             


Thr Gln  Pro Leu Tyr Arg Gly  Glu Leu Asn Glu His  Leu Gly Leu 
    1745                 1750                 1755             


Leu Gly  Pro Tyr Ile Arg Ala  Glu Val Glu Asp Asn  Ile Met Val 
    1760                 1765                 1770             


Thr Phe  Arg Asn Gln Ala Ser  Arg Pro Tyr Ser Phe  Tyr Ser Ser 
    1775                 1780                 1785             


Leu Ile  Ser Tyr Glu Glu Asp  Gln Arg Gln Gly Ala  Glu Pro Arg 
    1790                 1795                 1800             


Lys Asn  Phe Val Lys Pro Asn  Glu Thr Lys Thr Tyr  Phe Trp Lys 
    1805                 1810                 1815             


Val Gln  His His Met Ala Pro  Thr Lys Asp Glu Phe  Asp Cys Lys 
    1820                 1825                 1830             


Ala Trp  Ala Tyr Phe Ser Asp  Val Asp Leu Glu Lys  Asp Val His 
    1835                 1840                 1845             


Ser Gly  Leu Ile Gly Pro Leu  Leu Val Cys His Thr  Asn Thr Leu 
    1850                 1855                 1860             


Asn Pro  Ala His Gly Arg Gln  Val Thr Val Gln Glu  Phe Ala Leu 
    1865                 1870                 1875             


Phe Phe  Thr Ile Phe Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu 
    1880                 1885                 1890             


Asn Met  Glu Arg Asn Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu 
    1895                 1900                 1905             


Asp Pro  Thr Phe Lys Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly 
    1910                 1915                 1920             


Tyr Ile  Met Asp Thr Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln 
    1925                 1930                 1935             


Arg Ile  Arg Trp Tyr Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile 
    1940                 1945                 1950             


His Ser  Ile His Phe Ser Gly  His Val Phe Thr Val  Arg Lys Lys 
    1955                 1960                 1965             


Glu Glu  Tyr Lys Met Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe 
    1970                 1975                 1980             


Glu Thr  Val Glu Met Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val 
    1985                 1990                 1995             


Glu Cys  Leu Ile Gly Glu His  Leu His Ala Gly Met  Ser Thr Leu 
    2000                 2005                 2010             


Phe Leu  Val Tyr Ser Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala 
    2015                 2020                 2025             


Ser Gly  His Ile Arg Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr 
    2030                 2035                 2040             


Gly Gln  Trp Ala Pro Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser 
    2045                 2050                 2055             


Ile Asn  Ala Trp Ser Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val 
    2060                 2065                 2070             


Asp Leu  Leu Ala Pro Met Ile  Ile His Gly Ile Lys  Thr Gln Gly 
    2075                 2080                 2085             


Ala Arg  Gln Lys Phe Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile 
    2090                 2095                 2100             


Met Tyr  Ser Leu Asp Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn 
    2105                 2110                 2115             


Ser Thr  Gly Thr Leu Met Val  Phe Phe Gly Asn Val  Asp Ser Ser 
    2120                 2125                 2130             


Gly Ile  Lys His Asn Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr 
    2135                 2140                 2145             


Ile Arg  Leu His Pro Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg 
    2150                 2155                 2160             


Met Glu  Leu Met Gly Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu 
    2165                 2170                 2175             


Gly Met  Glu Ser Lys Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser 
    2180                 2185                 2190             


Ser Tyr  Phe Thr Asn Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala 
    2195                 2200                 2205             


Arg Leu  His Leu Gln Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val 
    2210                 2215                 2220             


Asn Asn  Pro Lys Glu Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met 
    2225                 2230                 2235             


Lys Val  Thr Gly Val Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr 
    2240                 2245                 2250             


Ser Met  Tyr Val Lys Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly 
    2255                 2260                 2265             


His Gln  Trp Thr Leu Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe 
    2270                 2275                 2280             


Gln Gly  Asn Gln Asp Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp 
    2285                 2290                 2295             


Pro Pro  Leu Leu Thr Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp 
    2300                 2305                 2310             


Val His  Gln Ile Ala Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala 
    2315                 2320                 2325             


Gln Asp  Leu Tyr 
    2330         


<210>  2
<211>  1438
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  BDD FVIII

<400>  2

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile Ala Lys Pro 
    50                  55                  60                  


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


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


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp Ala Ala Ser 
    210                 215                 220                 


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
        275                 280                 285             


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu Lys Arg His 
            740                 745                 750         


Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile 
        755                 760                 765             


Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp 
    770                 775                 780                 


Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys 
785                 790                 795                 800 


Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly 
                805                 810                 815     


Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser 
            820                 825                 830         


Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser 
        835                 840                 845             


Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu 
    850                 855                 860                 


Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr 
865                 870                 875                 880 


Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile 
                885                 890                 895     


Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe 
            900                 905                 910         


Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His 
        915                 920                 925             


Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe 
    930                 935                 940                 


Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro 
945                 950                 955                 960 


Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln 
                965                 970                 975     


Val Thr Val Gln Glu Phe Ala Leu Phe Leu Thr Ile Phe Asp Glu Thr 
            980                 985                 990         


Lys Ser Trp Tyr Phe Thr Glu Asn  Met Glu Arg Asn Cys  Arg Ala Pro 
        995                 1000                 1005             


Cys Asn  Ile Gln Met Glu Asp  Pro Thr Phe Lys Glu  Asn Tyr Arg 
    1010                 1015                 1020             


Phe His  Ala Ile Asn Gly Tyr  Ile Met Asp Thr Leu  Pro Gly Leu 
    1025                 1030                 1035             


Val Met  Ala Gln Asp Gln Arg  Ile Arg Trp Tyr Leu  Leu Ser Met 
    1040                 1045                 1050             


Gly Ser  Asn Glu Asn Ile His  Ser Ile His Phe Ser  Gly His Val 
    1055                 1060                 1065             


Phe Thr  Val Arg Lys Lys Glu  Glu Tyr Lys Met Ala  Leu Tyr Asn 
    1070                 1075                 1080             


Leu Tyr  Pro Gly Val Phe Glu  Thr Val Glu Met Leu  Pro Ser Lys 
    1085                 1090                 1095             


Ala Gly  Ile Trp Arg Val Glu  Cys Leu Ile Gly Glu  His Leu His 
    1100                 1105                 1110             


Ala Gly  Met Ser Thr Leu Phe  Leu Val Tyr Ser Asn  Lys Cys Gln 
    1115                 1120                 1125             


Thr Pro  Leu Gly Met Ala Ser  Gly His Ile Arg Asp  Phe Gln Ile 
    1130                 1135                 1140             


Thr Ala  Ser Gly Gln Tyr Gly  Gln Trp Ala Pro Lys  Leu Ala Arg 
    1145                 1150                 1155             


Leu His  Tyr Ser Gly Ser Ile  Asn Ala Trp Ser Thr  Lys Glu Pro 
    1160                 1165                 1170             


Phe Ser  Trp Ile Lys Val Asp  Leu Leu Ala Pro Met  Ile Ile His 
    1175                 1180                 1185             


Gly Ile  Lys Thr Gln Gly Ala  Arg Gln Lys Phe Ser  Ser Leu Tyr 
    1190                 1195                 1200             


Ile Ser  Gln Phe Ile Ile Met  Tyr Ser Leu Asp Gly  Lys Lys Trp 
    1205                 1210                 1215             


Gln Thr  Tyr Arg Gly Asn Ser  Thr Gly Thr Leu Met  Val Phe Phe 
    1220                 1225                 1230             


Gly Asn  Val Asp Ser Ser Gly  Ile Lys His Asn Ile  Phe Asn Pro 
    1235                 1240                 1245             


Pro Ile  Ile Ala Arg Tyr Ile  Arg Leu His Pro Thr  His Tyr Ser 
    1250                 1255                 1260             


Ile Arg  Ser Thr Leu Arg Met  Glu Leu Met Gly Cys  Asp Leu Asn 
    1265                 1270                 1275             


Ser Cys  Ser Met Pro Leu Gly  Met Glu Ser Lys Ala  Ile Ser Asp 
    1280                 1285                 1290             


Ala Gln  Ile Thr Ala Ser Ser  Tyr Phe Thr Asn Met  Phe Ala Thr 
    1295                 1300                 1305             


Trp Ser  Pro Ser Lys Ala Arg  Leu His Leu Gln Gly  Arg Ser Asn 
    1310                 1315                 1320             


Ala Trp  Arg Pro Gln Val Asn  Asn Pro Lys Glu Trp  Leu Gln Val 
    1325                 1330                 1335             


Asp Phe  Gln Lys Thr Met Lys  Val Thr Gly Val Thr  Thr Gln Gly 
    1340                 1345                 1350             


Val Lys  Ser Leu Leu Thr Ser  Met Tyr Val Lys Glu  Phe Leu Ile 
    1355                 1360                 1365             


Ser Ser  Ser Gln Asp Gly His  Gln Trp Thr Leu Phe  Phe Gln Asn 
    1370                 1375                 1380             


Gly Lys  Val Lys Val Phe Gln  Gly Asn Gln Asp Ser  Phe Thr Pro 
    1385                 1390                 1395             


Val Val  Asn Ser Leu Asp Pro  Pro Leu Leu Thr Arg  Tyr Leu Arg 
    1400                 1405                 1410             


Ile His  Pro Gln Ser Trp Val  His Gln Ile Ala Leu  Arg Met Glu 
    1415                 1420                 1425             


Val Leu  Gly Cys Glu Ala Gln  Asp Leu Tyr 
    1430                 1435             


<210>  3
<211>  754
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  BDD FVIII

<400>  3

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile Ala Lys Pro 
    50                  55                  60                  


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


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


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp Ala Ala Ser 
    210                 215                 220                 


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
        275                 280                 285             


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu Lys Arg His 
            740                 745                 750         


Gln Arg 
        


<210>  4
<211>  684
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  BDD FVIII

<400>  4

Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp Tyr 
1               5                   10                  15      


Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile Tyr 
            20                  25                  30          


Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr Arg 
        35                  40                  45              


His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met Ser 
    50                  55                  60                  


Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val Pro 
65                  70                  75                  80  


Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe Thr 
                85                  90                  95      


Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu Gly 
            100                 105                 110         


Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe Arg 
        115                 120                 125             


Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser Tyr 
    130                 135                 140                 


Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val Lys 
145                 150                 155                 160 


Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His Met Ala 
                165                 170                 175     


Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser Asp 
            180                 185                 190         


Val Asp Leu Glu Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu Leu 
        195                 200                 205             


Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln Val Thr 
    210                 215                 220                 


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


Trp Tyr Phe Thr Glu Asn Met Glu Arg Asn Cys Arg Ala Pro Cys Asn 
                245                 250                 255     


Ile Gln Met Glu Asp Pro Thr Phe Lys Glu Asn Tyr Arg Phe His Ala 
            260                 265                 270         


Ile Asn Gly Tyr Ile Met Asp Thr Leu Pro Gly Leu Val Met Ala Gln 
        275                 280                 285             


Asp Gln Arg Ile Arg Trp Tyr Leu Leu Ser Met Gly Ser Asn Glu Asn 
    290                 295                 300                 


Ile His Ser Ile His Phe Ser Gly His Val Phe Thr Val Arg Lys Lys 
305                 310                 315                 320 


Glu Glu Tyr Lys Met Ala Leu Tyr Asn Leu Tyr Pro Gly Val Phe Glu 
                325                 330                 335     


Thr Val Glu Met Leu Pro Ser Lys Ala Gly Ile Trp Arg Val Glu Cys 
            340                 345                 350         


Leu Ile Gly Glu His Leu His Ala Gly Met Ser Thr Leu Phe Leu Val 
        355                 360                 365             


Tyr Ser Asn Lys Cys Gln Thr Pro Leu Gly Met Ala Ser Gly His Ile 
    370                 375                 380                 


Arg Asp Phe Gln Ile Thr Ala Ser Gly Gln Tyr Gly Gln Trp Ala Pro 
385                 390                 395                 400 


Lys Leu Ala Arg Leu His Tyr Ser Gly Ser Ile Asn Ala Trp Ser Thr 
                405                 410                 415     


Lys Glu Pro Phe Ser Trp Ile Lys Val Asp Leu Leu Ala Pro Met Ile 
            420                 425                 430         


Ile His Gly Ile Lys Thr Gln Gly Ala Arg Gln Lys Phe Ser Ser Leu 
        435                 440                 445             


Tyr Ile Ser Gln Phe Ile Ile Met Tyr Ser Leu Asp Gly Lys Lys Trp 
    450                 455                 460                 


Gln Thr Tyr Arg Gly Asn Ser Thr Gly Thr Leu Met Val Phe Phe Gly 
465                 470                 475                 480 


Asn Val Asp Ser Ser Gly Ile Lys His Asn Ile Phe Asn Pro Pro Ile 
                485                 490                 495     


Ile Ala Arg Tyr Ile Arg Leu His Pro Thr His Tyr Ser Ile Arg Ser 
            500                 505                 510         


Thr Leu Arg Met Glu Leu Met Gly Cys Asp Leu Asn Ser Cys Ser Met 
        515                 520                 525             


Pro Leu Gly Met Glu Ser Lys Ala Ile Ser Asp Ala Gln Ile Thr Ala 
    530                 535                 540                 


Ser Ser Tyr Phe Thr Asn Met Phe Ala Thr Trp Ser Pro Ser Lys Ala 
545                 550                 555                 560 


Arg Leu His Leu Gln Gly Arg Ser Asn Ala Trp Arg Pro Gln Val Asn 
                565                 570                 575     


Asn Pro Lys Glu Trp Leu Gln Val Asp Phe Gln Lys Thr Met Lys Val 
            580                 585                 590         


Thr Gly Val Thr Thr Gln Gly Val Lys Ser Leu Leu Thr Ser Met Tyr 
        595                 600                 605             


Val Lys Glu Phe Leu Ile Ser Ser Ser Gln Asp Gly His Gln Trp Thr 
    610                 615                 620                 


Leu Phe Phe Gln Asn Gly Lys Val Lys Val Phe Gln Gly Asn Gln Asp 
625                 630                 635                 640 


Ser Phe Thr Pro Val Val Asn Ser Leu Asp Pro Pro Leu Leu Thr Arg 
                645                 650                 655     


Tyr Leu Arg Ile His Pro Gln Ser Trp Val His Gln Ile Ala Leu Arg 
            660                 665                 670         


Met Glu Val Leu Gly Cys Glu Ala Gln Asp Leu Tyr 
        675                 680                 


<210>  5
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Partial B domain

<400>  5

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


<210>  6
<211>  9048
<212>  DNA
<213>  Homo sapiens

<400>  6
gcttagtgct gagcacatcc agtgggtaaa gttccttaaa atgctctgca aagaaattgg       60

gacttttcat taaatcagaa attttacttt tttcccctcc tgggagctaa agatatttta      120

gagaagaatt aaccttttgc ttctccagtt gaacatttgt agcaataagt catgcaaata      180

gagctctcca cctgcttctt tctgtgcctt ttgcgattct gctttagtgc caccagaaga      240

tactacctgg gtgcagtgga actgtcatgg gactatatgc aaagtgatct cggtgagctg      300

cctgtggacg caagatttcc tcctagagtg ccaaaatctt ttccattcaa cacctcagtc      360

gtgtacaaaa agactctgtt tgtagaattc acggatcacc ttttcaacat cgctaagcca      420

aggccaccct ggatgggtct gctaggtcct accatccagg ctgaggttta tgatacagtg      480

gtcattacac ttaagaacat ggcttcccat cctgtcagtc ttcatgctgt tggtgtatcc      540

tactggaaag cttctgaggg agctgaatat gatgatcaga ccagtcaaag ggagaaagaa      600

gatgataaag tcttccctgg tggaagccat acatatgtct ggcaggtcct gaaagagaat      660

ggtccaatgg cctctgaccc actgtgcctt acctactcat atctttctca tgtggacctg      720

gtaaaagact tgaattcagg cctcattgga gccctactag tatgtagaga agggagtctg      780

gccaaggaaa agacacagac cttgcacaaa tttatactac tttttgctgt atttgatgaa      840

gggaaaagtt ggcactcaga aacaaagaac tccttgatgc aggataggga tgctgcatct      900

gctcgggcct ggcctaaaat gcacacagtc aatggttatg taaacaggtc tctgccaggt      960

ctgattggat gccacaggaa atcagtctat tggcatgtga ttggaatggg caccactcct     1020

gaagtgcact caatattcct cgaaggtcac acatttcttg tgaggaacca tcgccaggcg     1080

tccttggaaa tctcgccaat aactttcctt actgctcaaa cactcttgat ggaccttgga     1140

cagtttctac tgttttgtca tatctcttcc caccaacatg atggcatgga agcttatgtc     1200

aaagtagaca gctgtccaga ggaaccccaa ctacgaatga aaaataatga agaagcggaa     1260

gactatgatg atgatcttac tgattctgaa atggatgtgg tcaggtttga tgatgacaac     1320

tctccttcct ttatccaaat tcgctcagtt gccaagaagc atcctaaaac ttgggtacat     1380

tacattgctg ctgaagagga ggactgggac tatgctccct tagtcctcgc ccccgatgac     1440

agaagttata aaagtcaata tttgaacaat ggccctcagc ggattggtag gaagtacaaa     1500

aaagtccgat ttatggcata cacagatgaa acctttaaga ctcgtgaagc tattcagcat     1560

gaatcaggaa tcttgggacc tttactttat ggggaagttg gagacacact gttgattata     1620

tttaagaatc aagcaagcag accatataac atctaccctc acggaatcac tgatgtccgt     1680

cctttgtatt caaggagatt accaaaaggt gtaaaacatt tgaaggattt tccaattctg     1740

ccaggagaaa tattcaaata taaatggaca gtgactgtag aagatgggcc aactaaatca     1800

gatcctcggt gcctgacccg ctattactct agtttcgtta atatggagag agatctagct     1860

tcaggactca ttggccctct cctcatctgc tacaaagaat ctgtagatca aagaggaaac     1920

cagataatgt cagacaagag gaatgtcatc ctgttttctg tatttgatga gaaccgaagc     1980

tggtacctca cagagaatat acaacgcttt ctccccaatc cagctggagt gcagcttgag     2040

gatccagagt tccaagcctc caacatcatg cacagcatca atggctatgt ttttgatagt     2100

ttgcagttgt cagtttgttt gcatgaggtg gcatactggt acattctaag cattggagca     2160

cagactgact tcctttctgt cttcttctct ggatatacct tcaaacacaa aatggtctat     2220

gaagacacac tcaccctatt cccattctca ggagaaactg tcttcatgtc gatggaaaac     2280

ccaggtctat ggattctggg gtgccacaac tcagactttc ggaacagagg catgaccgcc     2340

ttactgaagg tttctagttg tgacaagaac actggtgatt attacgagga cagttatgaa     2400

gatatttcag catacttgct gagtaaaaac aatgccattg aaccaagaag cttctcccag     2460

aattcaagac accctagcac taggcaaaag caatttaatg ccaccacaat tccagaaaat     2520

gacatagaga agactgaccc ttggtttgca cacagaacac ctatgcctaa aatacaaaat     2580

gtctcctcta gtgatttgtt gatgctcttg cgacagagtc ctactccaca tgggctatcc     2640

ttatctgatc tccaagaagc caaatatgag actttttctg atgatccatc acctggagca     2700

atagacagta ataacagcct gtctgaaatg acacacttca ggccacagct ccatcacagt     2760

ggggacatgg tatttacccc tgagtcaggc ctccaattaa gattaaatga gaaactgggg     2820

acaactgcag caacagagtt gaagaaactt gatttcaaag tttctagtac atcaaataat     2880

ctgatttcaa caattccatc agacaatttg gcagcaggta ctgataatac aagttcctta     2940

ggacccccaa gtatgccagt tcattatgat agtcaattag ataccactct atttggcaaa     3000

aagtcatctc cccttactga gtctggtgga cctctgagct tgagtgaaga aaataatgat     3060

tcaaagttgt tagaatcagg tttaatgaat agccaagaaa gttcatgggg aaaaaatgta     3120

tcgtcaacag agagtggtag gttatttaaa gggaaaagag ctcatggacc tgctttgttg     3180

actaaagata atgccttatt caaagttagc atctctttgt taaagacaaa caaaacttcc     3240

aataattcag caactaatag aaagactcac attgatggcc catcattatt aattgagaat     3300

agtccatcag tctggcaaaa tatattagaa agtgacactg agtttaaaaa agtgacacct     3360

ttgattcatg acagaatgct tatggacaaa aatgctacag ctttgaggct aaatcatatg     3420

tcaaataaaa ctacttcatc aaaaaacatg gaaatggtcc aacagaaaaa agagggcccc     3480

attccaccag atgcacaaaa tccagatatg tcgttcttta agatgctatt cttgccagaa     3540

tcagcaaggt ggatacaaag gactcatgga aagaactctc tgaactctgg gcaaggcccc     3600

agtccaaagc aattagtatc cttaggacca gaaaaatctg tggaaggtca gaatttcttg     3660

tctgagaaaa acaaagtggt agtaggaaag ggtgaattta caaaggacgt aggactcaaa     3720

gagatggttt ttccaagcag cagaaaccta tttcttacta acttggataa tttacatgaa     3780

aataatacac acaatcaaga aaaaaaaatt caggaagaaa tagaaaagaa ggaaacatta     3840

atccaagaga atgtagtttt gcctcagata catacagtga ctggcactaa gaatttcatg     3900

aagaaccttt tcttactgag cactaggcaa aatgtagaag gttcatatga cggggcatat     3960

gctccagtac ttcaagattt taggtcatta aatgattcaa caaatagaac aaagaaacac     4020

acagctcatt tctcaaaaaa aggggaggaa gaaaacttgg aaggcttggg aaatcaaacc     4080

aagcaaattg tagagaaata tgcatgcacc acaaggatat ctcctaatac aagccagcag     4140

aattttgtca cgcaacgtag taagagagct ttgaaacaat tcagactccc actagaagaa     4200

acagaacttg aaaaaaggat aattgtggat gacacctcaa cccagtggtc caaaaacatg     4260

aaacatttga ccccgagcac cctcacacag atagactaca atgagaagga gaaaggggcc     4320

attactcagt ctcccttatc agattgcctt acgaggagtc atagcatccc tcaagcaaat     4380

agatctccat tacccattgc aaaggtatca tcatttccat ctattagacc tatatatctg     4440

accagggtcc tattccaaga caactcttct catcttccag cagcatctta tagaaagaaa     4500

gattctgggg tccaagaaag cagtcatttc ttacaaggag ccaaaaaaaa taacctttct     4560

ttagccattc taaccttgga gatgactggt gatcaaagag aggttggctc cctggggaca     4620

agtgccacaa attcagtcac atacaagaaa gttgagaaca ctgttctccc gaaaccagac     4680

ttgcccaaaa catctggcaa agttgaattg cttccaaaag ttcacattta tcagaaggac     4740

ctattcccta cggaaactag caatgggtct cctggccatc tggatctcgt ggaagggagc     4800

cttcttcagg gaacagaggg agcgattaag tggaatgaag caaacagacc tggaaaagtt     4860

ccctttctga gagtagcaac agaaagctct gcaaagactc cctccaagct attggatcct     4920

cttgcttggg ataaccacta tggtactcag ataccaaaag aagagtggaa atcccaagag     4980

aagtcaccag aaaaaacagc ttttaagaaa aaggatacca ttttgtccct gaacgcttgt     5040

gaaagcaatc atgcaatagc agcaataaat gagggacaaa ataagcccga aatagaagtc     5100

acctgggcaa agcaaggtag gactgaaagg ctgtgctctc aaaacccacc agtcttgaaa     5160

cgccatcaac gggaaataac tcgtactact cttcagtcag atcaagagga aattgactat     5220

gatgatacca tatcagttga aatgaagaag gaagattttg acatttatga tgaggatgaa     5280

aatcagagcc cccgcagctt tcaaaagaaa acacgacact attttattgc tgcagtggag     5340

aggctctggg attatgggat gagtagctcc ccacatgttc taagaaacag ggctcagagt     5400

ggcagtgtcc ctcagttcaa gaaagttgtt ttccaggaat ttactgatgg ctcctttact     5460

cagcccttat accgtggaga actaaatgaa catttgggac tcctggggcc atatataaga     5520

gcagaagttg aagataatat catggtaact ttcagaaatc aggcctctcg tccctattcc     5580

ttctattcta gccttatttc ttatgaggaa gatcagaggc aaggagcaga acctagaaaa     5640

aactttgtca agcctaatga aaccaaaact tacttttgga aagtgcaaca tcatatggca     5700

cccactaaag atgagtttga ctgcaaagcc tgggcttatt tctctgatgt tgacctggaa     5760

aaagatgtgc actcaggcct gattggaccc cttctggtct gccacactaa cacactgaac     5820

cctgctcatg ggagacaagt gacagtacag gaatttgctc tgtttttcac catctttgat     5880

gagaccaaaa gctggtactt cactgaaaat atggaaagaa actgcagggc tccctgcaat     5940

atccagatgg aagatcccac ttttaaagag aattatcgct tccatgcaat caatggctac     6000

ataatggata cactacctgg cttagtaatg gctcaggatc aaaggattcg atggtatctg     6060

ctcagcatgg gcagcaatga aaacatccat tctattcatt tcagtggaca tgtgttcact     6120

gtacgaaaaa aagaggagta taaaatggca ctgtacaatc tctatccagg tgtttttgag     6180

acagtggaaa tgttaccatc caaagctgga atttggcggg tggaatgcct tattggcgag     6240

catctacatg ctgggatgag cacacttttt ctggtgtaca gcaataagtg tcagactccc     6300

ctgggaatgg cttctggaca cattagagat tttcagatta cagcttcagg acaatatgga     6360

cagtgggccc caaagctggc cagacttcat tattccggat caatcaatgc ctggagcacc     6420

aaggagccct tttcttggat caaggtggat ctgttggcac caatgattat tcacggcatc     6480

aagacccagg gtgcccgtca gaagttctcc agcctctaca tctctcagtt tatcatcatg     6540

tatagtcttg atgggaagaa gtggcagact tatcgaggaa attccactgg aaccttaatg     6600

gtcttctttg gcaatgtgga ttcatctggg ataaaacaca atatttttaa ccctccaatt     6660

attgctcgat acatccgttt gcacccaact cattatagca ttcgcagcac tcttcgcatg     6720

gagttgatgg gctgtgattt aaatagttgc agcatgccat tgggaatgga gagtaaagca     6780

atatcagatg cacagattac tgcttcatcc tactttacca atatgtttgc cacctggtct     6840

ccttcaaaag ctcgacttca cctccaaggg aggagtaatg cctggagacc tcaggtgaat     6900

aatccaaaag agtggctgca agtggacttc cagaagacaa tgaaagtcac aggagtaact     6960

actcagggag taaaatctct gcttaccagc atgtatgtga aggagttcct catctccagc     7020

agtcaagatg gccatcagtg gactctcttt tttcagaatg gcaaagtaaa ggtttttcag     7080

ggaaatcaag actccttcac acctgtggtg aactctctag acccaccgtt actgactcgc     7140

taccttcgaa ttcaccccca gagttgggtg caccagattg ccctgaggat ggaggttctg     7200

ggctgcgagg cacaggacct ctactgaggg tggccactgc agcacctgcc actgccgtca     7260

cctctccctc ctcagctcca gggcagtgtc cctccctggc ttgccttcta cctttgtgct     7320

aaatcctagc agacactgcc ttgaagcctc ctgaattaac tatcatcagt cctgcatttc     7380

tttggtgggg ggccaggagg gtgcatccaa tttaacttaa ctcttaccta ttttctgcag     7440

ctgctcccag attactcctt ccttccaata taactaggca aaaagaagtg aggagaaacc     7500

tgcatgaaag cattcttccc tgaaaagtta ggcctctcag agtcaccact tcctctgttg     7560

tagaaaaact atgtgatgaa actttgaaaa agatatttat gatgttaaca tttcaggtta     7620

agcctcatac gtttaaaata aaactctcag ttgtttatta tcctgatcaa gcatggaaca     7680

aagcatgttt caggatcaga tcaatacaat cttggagtca aaaggcaaat catttggaca     7740

atctgcaaaa tggagagaat acaataacta ctacagtaaa gtctgtttct gcttccttac     7800

acatagatat aattatgtta tttagtcatt atgaggggca cattcttatc tccaaaacta     7860

gcattcttaa actgagaatt atagatgggg ttcaagaatc cctaagtccc ctgaaattat     7920

ataaggcatt ctgtataaat gcaaatgtgc atttttctga cgagtgtcca tagatataaa     7980

gccatttggt cttaattctg accaataaaa aaataagtca ggaggatgca attgttgaaa     8040

gctttgaaat aaaataacaa tgtcttcttg aaatttgtga tggccaagaa agaaaatgat     8100

gatgacatta ggcttctaaa ggacatacat ttaatatttc tgtggaaata tgaggaaaat     8160

ccatggttat ctgagatagg agatacaaac tttgtaattc taataatgca ctcagtttac     8220

tctctccctc tactaatttc ctgctgaaaa taacacaaca aaaatgtaac aggggaaatt     8280

atataccgtg actgaaaact agagtcctac ttacatagtt gaaatatcaa ggaggtcaga     8340

agaaaattgg actggtgaaa acagaaaaaa cactccagtc tgccatatca ccacacaata     8400

ggatccccct tcttgccctc cacccccata agattgtgaa gggtttactg ctccttccat     8460

ctgcctgacc ccttcactat gactacacag aatctcctga tagtaaaggg ggctggaggc     8520

aaggataagt tatagagcag ttggaggaag catccaaaga ttgcaaccca gggcaaatgg     8580

aaaacaggag atcctaatat gaaagaaaaa tggatcccaa tctgagaaaa ggcaaaagaa     8640

tggctacttt tttctatgct ggagtatttt ctaataatcc tgcttgaccc ttatctgacc     8700

tctttggaaa ctataacata gctgtcacag tatagtcaca atccacaaat gatgcaggtg     8760

caaatggttt atagccctgt gaagttctta aagtttagag gctaacttac agaaatgaat     8820

aagttgtttt gttttatagc ccggtagagg agttaacccc aaaggtgata tggttttatt     8880

tcctgttatg tttaacttga taatcttatt ttggcattct tttcccattg actatataca     8940

tctctatttc tcaaatgttc atggaactag ctcttttatt ttcctgctgg tttcttcagt     9000

aatgagttaa ataaaacatt gacacataca aacaaaaaaa aaaaaaaa                  9048


<210>  7
<211>  4410
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  BDD FVIII cDNA

<400>  7
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgggcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctaccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctctcaga atccaccagt cttgaaacgc catcaacggg aaataactcg tactactctt     2340

cagtcagatc aagaggaaat tgactatgat gataccatat cagttgaaat gaagaaggaa     2400

gattttgaca tttatgatga ggatgaaaat cagagccccc gcagctttca aaagaaaaca     2460

cgacactatt ttattgctgc agtggagagg ctctgggatt atgggatgag tagctcccca     2520

catgttctaa gaaacagggc tcagagtggc agtgtccctc agttcaagaa agttgttttc     2580

caggaattta ctgatggctc ctttactcag cccttatacc gtggagaact aaatgaacat     2640

ttgggactcc tggggccata tataagagca gaagttgaag ataatatcat ggtaactttc     2700

agaaatcagg cctctcgtcc ctattccttc tattctagcc ttatttctta tgaggaagat     2760

cagaggcaag gagcagaacc tagaaaaaac tttgtcaagc ctaatgaaac caaaacttac     2820

ttttggaaag tgcaacatca tatggcaccc actaaagatg agtttgactg caaagcctgg     2880

gcttatttct ctgatgttga cctggaaaaa gatgtgcact caggcctgat tggacccctt     2940

ctggtctgcc acactaacac actgaaccct gctcatggga gacaagtgac agtacaggaa     3000

tttgctctgt ttctcaccat ctttgatgag accaaaagct ggtacttcac tgaaaatatg     3060

gaaagaaact gcagggctcc ctgcaatatc cagatggaag atcccacttt taaagagaat     3120

tatcgcttcc atgcaatcaa tggctacata atggatacac tacctggctt agtaatggct     3180

caggatcaaa ggattcgatg gtatctgctc agcatgggca gcaatgaaaa catccattct     3240

attcatttca gtggacatgt gttcactgta cgaaaaaaag aggagtataa aatggcactg     3300

tacaatctct atccaggtgt ttttgagaca gtggaaatgt taccatccaa agctggaatt     3360

tggcgggtgg aatgccttat tggcgagcat ctacatgctg ggatgagcac actttttctg     3420

gtgtacagca ataagtgtca gactcccctg ggaatggctt ctggacacat tagagatttt     3480

cagattacag cttcaggaca atatggacag tgggccccaa agctggccag acttcattat     3540

tccggatcaa tcaatgcctg gagcaccaag gagccctttt cttggatcaa ggtggatctg     3600

ttggcaccaa tgattattca cggcatcaag acccagggtg cccgtcagaa gttctccagc     3660

ctctacatct ctcagtttat catcatgtat agtcttgatg ggaagaagtg gcagacttat     3720

cgaggaaatt ccactggaac cttaatggtc ttctttggca atgtggattc atctgggata     3780

aaacacaata tttttaaccc tccaattatt gctcgataca tccgtttgca cccaactcat     3840

tatagcattc gcagcactct tcgcatggag ttgatgggct gtgatttaaa tagttgcagc     3900

atgccattgg gaatggagag taaagcaata tcagatgcac agattactgc ttcatcctac     3960

tttaccaata tgtttgccac ctggtctcct tcaaaagctc gacttcacct ccaagggagg     4020

agtaatgcct ggagacctca ggtgaataat ccaaaagagt ggctgcaagt ggacttccag     4080

aagacaatga aagtcacagg agtaactact cagggagtaa aatctctgct taccagcatg     4140

tatgtgaagg agttcctcat ctccagcagt caagatggcc atcagtggac tctctttttt     4200

cagaatggca aagtaaaggt ttttcaggga aatcaagact ccttcacacc tgtggtgaac     4260

tctctagacc caccgttact gactcgctac cttcgaattc acccccagag ttgggtgcac     4320

cagattgccc tgaggatgga ggttctgggc tgcgaggcac aggacctcta cggaggcggt     4380

ggggactaca aggacgatga cgacaagtaa                                      4410


<210>  8
<211>  4374
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  BDD FVIII cDNA

<400>  8
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgggcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctaccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctctcaga atccaccagt cttgaaacgc catcaacggg aaataactcg tactactctt     2340

cagtcagatc aagaggaaat tgactatgat gataccatat cagttgaaat gaagaaggaa     2400

gattttgaca tttatgatga ggatgaaaat cagagccccc gcagctttca aaagaaaaca     2460

cgacactatt ttattgctgc agtggagagg ctctgggatt atgggatgag tagctcccca     2520

catgttctaa gaaacagggc tcagagtggc agtgtccctc agttcaagaa agttgttttc     2580

caggaattta ctgatggctc ctttactcag cccttatacc gtggagaact aaatgaacat     2640

ttgggactcc tggggccata tataagagca gaagttgaag ataatatcat ggtaactttc     2700

agaaatcagg cctctcgtcc ctattccttc tattctagcc ttatttctta tgaggaagat     2760

cagaggcaag gagcagaacc tagaaaaaac tttgtcaagc ctaatgaaac caaaacttac     2820

ttttggaaag tgcaacatca tatggcaccc actaaagatg agtttgactg caaagcctgg     2880

gcttatttct ctgatgttga cctggaaaaa gatgtgcact caggcctgat tggacccctt     2940

ctggtctgcc acactaacac actgaaccct gctcatggga gacaagtgac agtacaggaa     3000

tttgctctgt ttctcaccat ctttgatgag accaaaagct ggtacttcac tgaaaatatg     3060

gaaagaaact gcagggctcc ctgcaatatc cagatggaag atcccacttt taaagagaat     3120

tatcgcttcc atgcaatcaa tggctacata atggatacac tacctggctt agtaatggct     3180

caggatcaaa ggattcgatg gtatctgctc agcatgggca gcaatgaaaa catccattct     3240

attcatttca gtggacatgt gttcactgta cgaaaaaaag aggagtataa aatggcactg     3300

tacaatctct atccaggtgt ttttgagaca gtggaaatgt taccatccaa agctggaatt     3360

tggcgggtgg aatgccttat tggcgagcat ctacatgctg ggatgagcac actttttctg     3420

gtgtacagca ataagtgtca gactcccctg ggaatggctt ctggacacat tagagatttt     3480

cagattacag cttcaggaca atatggacag tgggccccaa agctggccag acttcattat     3540

tccggatcaa tcaatgcctg gagcaccaag gagccctttt cttggatcaa ggtggatctg     3600

ttggcaccaa tgattattca cggcatcaag acccagggtg cccgtcagaa gttctccagc     3660

ctctacatct ctcagtttat catcatgtat agtcttgatg ggaagaagtg gcagacttat     3720

cgaggaaatt ccactggaac cttaatggtc ttctttggca atgtggattc atctgggata     3780

aaacacaata tttttaaccc tccaattatt gctcgataca tccgtttgca cccaactcat     3840

tatagcattc gcagcactct tcgcatggag ttgatgggct gtgatttaaa tagttgcagc     3900

atgccattgg gaatggagag taaagcaata tcagatgcac agattactgc ttcatcctac     3960

tttaccaata tgtttgccac ctggtctcct tcaaaagctc gacttcacct ccaagggagg     4020

agtaatgcct ggagacctca ggtgaataat ccaaaagagt ggctgcaagt ggacttccag     4080

aagacaatga aagtcacagg agtaactact cagggagtaa aatctctgct taccagcatg     4140

tatgtgaagg agttcctcat ctccagcagt caagatggcc atcagtggac tctctttttt     4200

cagaatggca aagtaaaggt ttttcaggga aatcaagact ccttcacacc tgtggtgaac     4260

tctctagacc caccgttact gactcgctac cttcgaattc acccccagag ttgggtgcac     4320

cagattgccc tgaggatgga ggttctgggc tgcgaggcac aggacctcta ctaa           4374


