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<110>  ԴҽҩƼϺ޹˾
       񻪣Ϻз޹˾
 
<120>  ͻ͵ѪVIIIںϵ׼Ʊ;

<130>  2018

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  2351
<212>  PRT
<213>  ȫFVIII

<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 
    1010                 1015                 1020             


Asn Asn  Ser Ala Thr Asn Arg  Lys Thr His Ile Asp  Gly Pro Ser 
    1025                 1030                 1035             


Leu Leu  Ile Glu Asn Ser Pro  Ser Val Trp Gln Asn  Ile Leu Glu 
    1040                 1045                 1050             


Ser Asp  Thr Glu Phe Lys Lys  Val Thr Pro Leu Ile  His Asp Arg 
    1055                 1060                 1065             


Met Leu  Met Asp Lys Asn Ala  Thr Ala Leu Arg Leu  Asn His Met 
    1070                 1075                 1080             


Ser Asn  Lys Thr Thr Ser Ser  Lys Asn Met Glu Met  Val Gln Gln 
    1085                 1090                 1095             


Lys Lys  Glu Gly Pro Ile Pro  Pro Asp Ala Gln Asn  Pro Asp Met 
    1100                 1105                 1110             


Ser Phe  Phe Lys Met Leu Phe  Leu Pro Glu Ser Ala  Arg Trp Ile 
    1115                 1120                 1125             


Gln Arg  Thr His Gly Lys Asn  Ser Leu Asn Ser Gly  Gln Gly Pro 
    1130                 1135                 1140             


Ser Pro  Lys Gln Leu Val Ser  Leu Gly Pro Glu Lys  Ser Val Glu 
    1145                 1150                 1155             


Gly Gln  Asn Phe Leu Ser Glu  Lys Asn Lys Val Val  Val Gly Lys 
    1160                 1165                 1170             


Gly Glu  Phe Thr Lys Asp Val  Gly Leu Lys Glu Met  Val Phe Pro 
    1175                 1180                 1185             


Ser Ser  Arg Asn Leu Phe Leu  Thr Asn Leu Asp Asn  Leu His Glu 
    1190                 1195                 1200             


Asn Asn  Thr His Asn Gln Glu  Lys Lys Ile Gln Glu  Glu Ile Glu 
    1205                 1210                 1215             


Lys Lys  Glu Thr Leu Ile Gln  Glu Asn Val Val Leu  Pro Gln Ile 
    1220                 1225                 1230             


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 
    1250                 1255                 1260             


Ala Pro  Val Leu Gln Asp Phe  Arg Ser Leu Asn Asp  Ser Thr Asn 
    1265                 1270                 1275             


Arg Thr  Lys Lys His Thr Ala  His Phe Ser Lys Lys  Gly Glu Glu 
    1280                 1285                 1290             


Glu Asn  Leu Glu Gly Leu Gly  Asn Gln Thr Lys Gln  Ile Val Glu 
    1295                 1300                 1305             


Lys Tyr  Ala Cys Thr Thr Arg  Ile Ser Pro Asn Thr  Ser Gln Gln 
    1310                 1315                 1320             


Asn Phe  Val Thr Gln Arg Ser  Lys Arg Ala Leu Lys  Gln Phe Arg 
    1325                 1330                 1335             


Leu Pro  Leu Glu Glu Thr Glu  Leu Glu Lys Arg Ile  Ile Val Asp 
    1340                 1345                 1350             


Asp Thr  Ser Thr Gln Trp Ser  Lys Asn Met Lys His  Leu Thr Pro 
    1355                 1360                 1365             


Ser Thr  Leu Thr Gln Ile Asp  Tyr Asn Glu Lys Glu  Lys Gly Ala 
    1370                 1375                 1380             


Ile Thr  Gln Ser Pro Leu Ser  Asp Cys Leu Thr Arg  Ser His Ser 
    1385                 1390                 1395             


Ile Pro  Gln Ala Asn Arg Ser  Pro Leu Pro Ile Ala  Lys Val Ser 
    1400                 1405                 1410             


Ser Phe  Pro Ser Ile Arg Pro  Ile Tyr Leu Thr Arg  Val Leu Phe 
    1415                 1420                 1425             


Gln Asp  Asn Ser Ser His Leu  Pro Ala Ala Ser Tyr  Arg Lys Lys 
    1430                 1435                 1440             


Asp Ser  Gly Val Gln Glu Ser  Ser His Phe Leu Gln  Gly Ala Lys 
    1445                 1450                 1455             


Lys Asn  Asn Leu Ser Leu Ala  Ile Leu Thr Leu Glu  Met Thr Gly 
    1460                 1465                 1470             


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 
    1490                 1495                 1500             


Leu Pro  Lys Thr Ser Gly Lys  Val Glu Leu Leu Pro  Lys Val His 
    1505                 1510                 1515             


Ile Tyr  Gln Lys Asp Leu Phe  Pro Thr Glu Thr Ser  Asn Gly Ser 
    1520                 1525                 1530             


Pro Gly  His Leu Asp Leu Val  Glu Gly Ser Leu Leu  Gln Gly Thr 
    1535                 1540                 1545             


Glu Gly  Ala Ile Lys Trp Asn  Glu Ala Asn Arg Pro  Gly Lys Val 
    1550                 1555                 1560             


Pro Phe  Leu Arg Val Ala Thr  Glu Ser Ser Ala Lys  Thr Pro Ser 
    1565                 1570                 1575             


Lys Leu  Leu Asp Pro Leu Ala  Trp Asp Asn His Tyr  Gly Thr Gln 
    1580                 1585                 1590             


Ile Pro  Lys Glu Glu Trp Lys  Ser Gln Glu Lys Ser  Pro Glu Lys 
    1595                 1600                 1605             


Thr Ala  Phe Lys Lys Lys Asp  Thr Ile Leu Ser Leu  Asn Ala Cys 
    1610                 1615                 1620             


Glu Ser  Asn His Ala Ile Ala  Ala Ile Asn Glu Gly  Gln Asn Lys 
    1625                 1630                 1635             


Pro Glu  Ile Glu Val Thr Trp  Ala Lys Gln Gly Arg  Thr Glu Arg 
    1640                 1645                 1650             


Leu Cys  Ser Gln Asn Pro Pro  Val Leu Lys Arg His  Gln Arg Glu 
    1655                 1660                 1665             


Ile Thr  Arg Thr Thr Leu Gln  Ser Asp Gln Glu Glu  Ile Asp Tyr 
    1670                 1675                 1680             


Asp Asp  Thr Ile Ser Val Glu  Met Lys Lys Glu Asp  Phe Asp Ile 
    1685                 1690                 1695             


Tyr Asp  Glu Asp Glu Asn Gln  Ser Pro Arg Ser Phe  Gln Lys Lys 
    1700                 1705                 1710             


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 
    1730                 1735                 1740             


Gly Ser  Val Pro Gln Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr 
    1745                 1750                 1755             


Asp Gly  Ser Phe Thr Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu 
    1760                 1765                 1770             


His Leu  Gly Leu Leu Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp 
    1775                 1780                 1785             


Asn Ile  Met Val Thr Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser 
    1790                 1795                 1800             


Phe Tyr  Ser Ser Leu Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly 
    1805                 1810                 1815             


Ala Glu  Pro Arg Lys Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr 
    1820                 1825                 1830             


Tyr Phe  Trp Lys Val Gln His  His Met Ala Pro Thr  Lys Asp Glu 
    1835                 1840                 1845             


Phe Asp  Cys Lys Ala Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu 
    1850                 1855                 1860             


Lys Asp  Val His Ser Gly Leu  Ile Gly Pro Leu Leu  Val Cys His 
    1865                 1870                 1875             


Thr Asn  Thr Leu Asn Pro Ala  His Gly Arg Gln Val  Thr Val Gln 
    1880                 1885                 1890             


Glu Phe  Ala Leu Phe Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp 
    1895                 1900                 1905             


Tyr Phe  Thr Glu Asn Met Glu  Arg Asn Cys Arg Ala  Pro Cys Asn 
    1910                 1915                 1920             


Ile Gln  Met Glu Asp Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His 
    1925                 1930                 1935             


Ala Ile  Asn Gly Tyr Ile Met  Asp Thr Leu Pro Gly  Leu Val Met 
    1940                 1945                 1950             


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 
    1970                 1975                 1980             


Val Arg  Lys Lys Glu Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr 
    1985                 1990                 1995             


Pro Gly  Val Phe Glu Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly 
    2000                 2005                 2010             


Ile Trp  Arg Val Glu Cys Leu  Ile Gly Glu His Leu  His Ala Gly 
    2015                 2020                 2025             


Met Ser  Thr Leu Phe Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro 
    2030                 2035                 2040             


Leu Gly  Met Ala Ser Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala 
    2045                 2050                 2055             


Ser Gly  Gln Tyr Gly Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His 
    2060                 2065                 2070             


Tyr Ser  Gly Ser Ile Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser 
    2075                 2080                 2085             


Trp Ile  Lys Val Asp Leu Leu  Ala Pro Met Ile Ile  His Gly Ile 
    2090                 2095                 2100             


Lys Thr  Gln Gly Ala Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser 
    2105                 2110                 2115             


Gln Phe  Ile Ile Met Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr 
    2120                 2125                 2130             


Tyr Arg  Gly Asn Ser Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn 
    2135                 2140                 2145             


Val Asp  Ser Ser Gly Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile 
    2150                 2155                 2160             


Ile Ala  Arg Tyr Ile Arg Leu  His Pro Thr His Tyr  Ser Ile Arg 
    2165                 2170                 2175             


Ser Thr  Leu Arg Met Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys 
    2180                 2185                 2190             


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 
    2210                 2215                 2220             


Pro Ser  Lys Ala Arg Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp 
    2225                 2230                 2235             


Arg Pro  Gln Val Asn Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe 
    2240                 2245                 2250             


Gln Lys  Thr Met Lys Val Thr  Gly Val Thr Thr Gln  Gly Val Lys 
    2255                 2260                 2265             


Ser Leu  Leu Thr Ser Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser 
    2270                 2275                 2280             


Ser Gln  Asp Gly His Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys 
    2285                 2290                 2295             


Val Lys  Val Phe Gln Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val 
    2300                 2305                 2310             


Asn Ser  Leu Asp Pro Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His 
    2315                 2320                 2325             


Pro Gln  Ser Trp Val His Gln  Ile Ala Leu Arg Met  Glu Val Leu 
    2330                 2335                 2340             


Gly Cys  Glu Ala Gln Asp Leu  Tyr 
    2345                 2350     


<210>  2
<211>  1445
<212>  PRT
<213>  scFVIII

<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 Ser Arg His Pro Ser Thr Arg 
            740                 745                 750         


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


Gln Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu 
    770                 775                 780                 


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


Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val 
                805                 810                 815     


Glu Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg 
            820                 825                 830         


Asn Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe 
        835                 840                 845             


Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu 
    850                 855                 860                 


Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val 
865                 870                 875                 880 


Glu Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr 
                885                 890                 895     


Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly 
            900                 905                 910         


Ala Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr 
        915                 920                 925             


Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp 
    930                 935                 940                 


Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val 
945                 950                 955                 960 


His Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu 
                965                 970                 975     


Asn Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe 
            980                 985                 990         


Phe Thr Ile Phe Asp Glu Thr Lys  Ser Trp Tyr Phe Thr  Glu Asn Met 
        995                 1000                 1005             


Glu Arg  Asn Cys Arg Ala Pro  Cys Asn Ile Gln Met  Glu Asp Pro 
    1010                 1015                 1020             


Thr Phe  Lys Glu Asn Tyr Arg  Phe His Ala Ile Asn  Gly Tyr Ile 
    1025                 1030                 1035             


Met Asp  Thr Leu Pro Gly Leu  Val Met Ala Gln Asp  Gln Arg Ile 
    1040                 1045                 1050             


Arg Trp  Tyr Leu Leu Ser Met  Gly Ser Asn Glu Asn  Ile His Ser 
    1055                 1060                 1065             


Ile His  Phe Ser Gly His Val  Phe Thr Val Arg Lys  Lys Glu Glu 
    1070                 1075                 1080             


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


Val Glu  Met Leu Pro Ser Lys  Ala Gly Ile Trp Arg  Val Glu Cys 
    1100                 1105                 1110             


Leu Ile  Gly Glu His Leu His  Ala Gly Met Ser Thr  Leu Phe Leu 
    1115                 1120                 1125             


Val Tyr  Ser Asn Lys Cys Gln  Thr Pro Leu Gly Met  Ala Ser Gly 
    1130                 1135                 1140             


His Ile  Arg Asp Phe Gln Ile  Thr Ala Ser Gly Gln  Tyr Gly Gln 
    1145                 1150                 1155             


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


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


Leu Ala  Pro Met Ile Ile His  Gly Ile Lys Thr Gln  Gly Ala Arg 
    1190                 1195                 1200             


Gln Lys  Phe Ser Ser Leu Tyr  Ile Ser Gln Phe Ile  Ile Met Tyr 
    1205                 1210                 1215             


Ser Leu  Asp Gly Lys Lys Trp  Gln Thr Tyr Arg Gly  Asn Ser Thr 
    1220                 1225                 1230             


Gly Thr  Leu Met Val Phe Phe  Gly Asn Val Asp Ser  Ser Gly Ile 
    1235                 1240                 1245             


Lys His  Asn Ile Phe Asn Pro  Pro Ile Ile Ala Arg  Tyr Ile Arg 
    1250                 1255                 1260             


Leu His  Pro Thr His Tyr Ser  Ile Arg Ser Thr Leu  Arg Met Glu 
    1265                 1270                 1275             


Leu Met  Gly Cys Asp Leu Asn  Ser Cys Ser Met Pro  Leu Gly Met 
    1280                 1285                 1290             


Glu Ser  Lys Ala Ile Ser Asp  Ala Gln Ile Thr Ala  Ser Ser Tyr 
    1295                 1300                 1305             


Phe Thr  Asn Met Phe Ala Thr  Trp Ser Pro Ser Lys  Ala Arg Leu 
    1310                 1315                 1320             


His Leu  Gln Gly Arg Ser Asn  Ala Trp Arg Pro Gln  Val Asn Asn 
    1325                 1330                 1335             


Pro Lys  Glu Trp Leu Gln Val  Asp Phe Gln Lys Thr  Met Lys Val 
    1340                 1345                 1350             


Thr Gly  Val Thr Thr Gln Gly  Val Lys Ser Leu Leu  Thr Ser Met 
    1355                 1360                 1365             


Tyr Val  Lys Glu Phe Leu Ile  Ser Ser Ser Gln Asp  Gly His Gln 
    1370                 1375                 1380             


Trp Thr  Leu Phe Phe Gln Asn  Gly Lys Val Lys Val  Phe Gln Gly 
    1385                 1390                 1395             


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


Leu Leu  Thr Arg Tyr Leu Arg  Ile His Pro Gln Ser  Trp Val His 
    1415                 1420                 1425             


Gln Ile  Ala Leu Arg Met Glu  Val Leu Gly Cys Glu  Ala Gln Asp 
    1430                 1435                 1440             


Leu Tyr  
    1445 


<210>  3
<211>  33
<212>  PRT
<213>  hCG CTPȫ

<400>  3

Pro Arg Phe Gln Asp Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu 
1               5                   10                  15      


Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro 
            20                  25                  30          


Gln 
    


<210>  4
<211>  227
<212>  PRT
<213>  vFc1

<400>  4

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Val Ala Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Ser Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


<210>  5
<211>  223
<212>  PRT
<213>  vFc2-1

<400>  5

Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val 
1               5                   10                  15      


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
            20                  25                  30          


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
        35                  40                  45              


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    50                  55                  60                  


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                85                  90                  95      


Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Ser Ile Glu Lys Thr Ile 
            100                 105                 110         


Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
        115                 120                 125             


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    130                 135                 140                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
145                 150                 155                 160 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
            180                 185                 190         


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        195                 200                 205             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220             


<210>  6
<211>  223
<212>  PRT
<213>  vFc2-2

<400>  6

Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val 
1               5                   10                  15      


Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr 
            20                  25                  30          


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
        35                  40                  45              


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    50                  55                  60                  


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                85                  90                  95      


Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile 
            100                 105                 110         


Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
        115                 120                 125             


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    130                 135                 140                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
145                 150                 155                 160 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
            180                 185                 190         


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu 
        195                 200                 205             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220             


<210>  7
<211>  223
<212>  PRT
<213>  vFc2-3

<400>  7

Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val 
1               5                   10                  15      


Phe Leu Phe Pro Pro Lys Pro Lys Asp Gln Leu Met Ile Ser Arg Thr 
            20                  25                  30          


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
        35                  40                  45              


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    50                  55                  60                  


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser 
65                  70                  75                  80  


Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                85                  90                  95      


Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Ser Ile Glu Lys Thr Ile 
            100                 105                 110         


Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
        115                 120                 125             


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    130                 135                 140                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
145                 150                 155                 160 


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


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
            180                 185                 190         


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Leu His Glu Ala Leu 
        195                 200                 205             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220             


<210>  8
<211>  229
<212>  PRT
<213>  vFc4

<400>  8

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe 
1               5                   10                  15      


Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         


Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 


Leu Ser Leu Gly Lys 
225                 


<210>  9
<211>  1723
<212>  PRT
<213>  scFVIIIںϵװ

<400>  9

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 Arg Thr Thr Leu 
        755                 760                 765             


Gln Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu 
    770                 775                 780                 


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


Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val 
                805                 810                 815     


Glu Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg 
            820                 825                 830         


Asn Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe 
        835                 840                 845             


Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu 
    850                 855                 860                 


Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val 
865                 870                 875                 880 


Glu Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr 
                885                 890                 895     


Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly 
            900                 905                 910         


Ala Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr 
        915                 920                 925             


Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp 
    930                 935                 940                 


Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val 
945                 950                 955                 960 


His Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu 
                965                 970                 975     


Asn Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe 
            980                 985                 990         


Phe Thr Ile Phe Asp Glu Thr Lys  Ser Trp Tyr Phe Thr  Glu Asn Met 
        995                 1000                 1005             


Glu Arg  Asn Cys Arg Ala Pro  Cys Asn Ile Gln Met  Glu Asp Pro 
    1010                 1015                 1020             


Thr Phe  Lys Glu Asn Tyr Arg  Phe His Ala Ile Asn  Gly Tyr Ile 
    1025                 1030                 1035             


Met Asp  Thr Leu Pro Gly Leu  Val Met Ala Gln Asp  Gln Arg Ile 
    1040                 1045                 1050             


Arg Trp  Tyr Leu Leu Ser Met  Gly Ser Asn Glu Asn  Ile His Ser 
    1055                 1060                 1065             


Ile His  Phe Ser Gly His Val  Phe Thr Val Arg Lys  Lys Glu Glu 
    1070                 1075                 1080             


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


Val Glu  Met Leu Pro Ser Lys  Ala Gly Ile Trp Arg  Val Glu Cys 
    1100                 1105                 1110             


Leu Ile  Gly Glu His Leu His  Ala Gly Met Ser Thr  Leu Phe Leu 
    1115                 1120                 1125             


Val Tyr  Ser Asn Lys Cys Gln  Thr Pro Leu Gly Met  Ala Ser Gly 
    1130                 1135                 1140             


His Ile  Arg Asp Phe Gln Ile  Thr Ala Ser Gly Gln  Tyr Gly Gln 
    1145                 1150                 1155             


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


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


Leu Ala  Pro Met Ile Ile His  Gly Ile Lys Thr Gln  Gly Ala Arg 
    1190                 1195                 1200             


Gln Lys  Phe Ser Ser Leu Tyr  Ile Ser Gln Phe Ile  Ile Met Tyr 
    1205                 1210                 1215             


Ser Leu  Asp Gly Lys Lys Trp  Gln Thr Tyr Arg Gly  Asn Ser Thr 
    1220                 1225                 1230             


Gly Thr  Leu Met Val Phe Phe  Gly Asn Val Asp Ser  Ser Gly Ile 
    1235                 1240                 1245             


Lys His  Asn Ile Phe Asn Pro  Pro Ile Ile Ala Arg  Tyr Ile Arg 
    1250                 1255                 1260             


Leu His  Pro Thr His Tyr Ser  Ile Arg Ser Thr Leu  Arg Met Glu 
    1265                 1270                 1275             


Leu Met  Gly Cys Asp Leu Asn  Ser Cys Ser Met Pro  Leu Gly Met 
    1280                 1285                 1290             


Glu Ser  Lys Ala Ile Ser Asp  Ala Gln Ile Thr Ala  Ser Ser Tyr 
    1295                 1300                 1305             


Phe Thr  Asn Met Phe Ala Thr  Trp Ser Pro Ser Lys  Ala Arg Leu 
    1310                 1315                 1320             


His Leu  Gln Gly Arg Ser Asn  Ala Trp Arg Pro Gln  Val Asn Asn 
    1325                 1330                 1335             


Pro Lys  Glu Trp Leu Gln Val  Asp Phe Gln Lys Thr  Met Lys Val 
    1340                 1345                 1350             


Thr Gly  Val Thr Thr Gln Gly  Val Lys Ser Leu Leu  Thr Ser Met 
    1355                 1360                 1365             


Tyr Val  Lys Glu Phe Leu Ile  Ser Ser Ser Gln Asp  Gly His Gln 
    1370                 1375                 1380             


Trp Thr  Leu Phe Phe Gln Asn  Gly Lys Val Lys Val  Phe Gln Gly 
    1385                 1390                 1395             


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


Leu Leu  Thr Arg Tyr Leu Arg  Ile His Pro Gln Ser  Trp Val His 
    1415                 1420                 1425             


Gln Ile  Ala Leu Arg Met Glu  Val Leu Gly Cys Glu  Ala Gln Asp 
    1430                 1435                 1440             


Leu Tyr  Gly Ser Gly Gly Gly  Gly Ser Gly Gly Gly  Gly Ser Gly 
    1445                 1450                 1455             


Gly Gly  Gly Ser Gly Gly Gly  Gly Ser Gly Gly Gly  Gly Ser Ser 
    1460                 1465                 1470             


Ser Ser  Ser Lys Ala Pro Pro  Pro Ser Leu Pro Ser  Pro Ser Arg 
    1475                 1480                 1485             


Leu Pro  Gly Pro Ser Asp Thr  Pro Ile Leu Pro Gln  Val Glu Cys 
    1490                 1495                 1500             


Pro Pro  Cys Pro Ala Pro Pro  Val Ala Gly Pro Ser  Val Phe Leu 
    1505                 1510                 1515             


Phe Pro  Pro Lys Pro Lys Asp  Gln Leu Met Ile Ser  Arg Thr Pro 
    1520                 1525                 1530             


Glu Val  Thr Cys Val Val Val  Asp Val Ser His Glu  Asp Pro Glu 
    1535                 1540                 1545             


Val Gln  Phe Asn Trp Tyr Val  Asp Gly Val Glu Val  His Asn Ala 
    1550                 1555                 1560             


Lys Thr  Lys Pro Arg Glu Glu  Gln Phe Asn Ser Thr  Phe Arg Val 
    1565                 1570                 1575             


Val Ser  Val Leu Thr Val Val  His Gln Asp Trp Leu  Asn Gly Lys 
    1580                 1585                 1590             


Glu Tyr  Lys Cys Lys Val Ser  Asn Lys Gly Leu Pro  Ala Ser Ile 
    1595                 1600                 1605             


Glu Lys  Thr Ile Ser Lys Thr  Lys Gly Gln Pro Arg  Glu Pro Gln 
    1610                 1615                 1620             


Val Tyr  Thr Leu Pro Pro Ser  Arg Glu Glu Met Thr  Lys Asn Gln 
    1625                 1630                 1635             


Val Ser  Leu Thr Cys Leu Val  Lys Gly Phe Tyr Pro  Ser Asp Ile 
    1640                 1645                 1650             


Ala Val  Glu Trp Glu Ser Asn  Gly Gln Pro Glu Asn  Asn Tyr Lys 
    1655                 1660                 1665             


Thr Thr  Pro Pro Met Leu Asp  Ser Asp Gly Ser Phe  Phe Leu Tyr 
    1670                 1675                 1680             


Ser Lys  Leu Thr Val Asp Lys  Ser Arg Trp Gln Gln  Gly Asn Val 
    1685                 1690                 1695             


Phe Ser  Cys Ser Val Leu His  Glu Ala Leu His Asn  His Tyr Thr 
    1700                 1705                 1710             


Gln Lys  Ser Leu Ser Leu Ser  Pro Gly Lys 
    1715                 1720             


<210>  10
<211>  5169
<212>  DNA
<213>  scFVIIIںϵ׺

<400>  10
gccaccagga ggtactacct cggagccgtc gagctcagct gggattatat gcagagcgac       60

ctcggagaac tccctgtcga tgccaggttt cccccccggg tgcccaagtc cttccccttt      120

aacacctccg tcgtctacaa gaagaccctg ttcgtcgagt tcacagacca tctgttcaat      180

attgctaaac ccaggccccc ctggatggga ctgctgggcc ccacaatcca agccgaggtg      240

tatgataccg tggtgatcac cctcaagaat atggcttccc atcccgtctc cctgcacgcc      300

gtcggcgtgt cctactggaa ggcctccgaa ggcgccgagt acgatgatca gacaagccag      360

cgggagaagg aggatgataa ggtctttccc ggaggttctc acacctatgt ctggcaggtg      420

ctgaaagaga acggccccat ggctagcgac cccctgtgcc tcacctattc ctacctcagc      480

catgtggacc tggtgaagga tctgaactcc ggcctgattg gcgccctcct ggtctgcagg      540

gagggaagcc tggccaaaga aaagacccag accctgcata aattcatcct cctgtttgcc      600

gtcttcgatg agggcaagtc ctggcactcc gaaacaaaga actccctgat gcaggacagg      660

gacgctgcct ccgccagggc ctggcccaag atgcacaccg tcaacggata cgtgaatagg      720

tccctccccg gcctgattgg atgccatcgg aagtccgtgt attggcacgt gatcggcatg      780

ggaaccacac ccgaagtgca ctccatcttc ctggaaggac atacatttct cgtccggaac      840

caccggcagg cttccctgga aatctcccct atcaccttcc tgaccgctca gacactgctg      900

atggatctgg gccagttcct gctgttctgc cacatttcct cccaccagca cgacggcatg      960

gaggcttatg tcaaggtgga tagctgcccc gaggaacccc agctgcggat gaaaaacaat     1020

gaggaagccg aggactacga cgatgacctc accgatagcg agatggacgt ggtcaggttc     1080

gacgacgata actccccttc cttcatccag atccggagcg tggccaagaa gcaccccaaa     1140

acctgggtgc actacatcgc cgctgaggag gaagactggg actatgctcc tctcgtgctg     1200

gcccccgatg acaggtccta caaaagccag tatctgaaca atggacccca gcggattgga     1260

aggaagtata agaaagtccg gtttatggct tacaccgacg agacctttaa aacccgggaa     1320

gccatccagc acgagagcgg catcctcggc cctctcctgt acggagaggt cggagacaca     1380

ctcctcatca tttttaagaa ccaggcctcc cggccctaca acatctatcc tcatggcatc     1440

accgatgtga ggcctctgta cagcaggagg ctgcccaaag gagtcaagca cctgaaagat     1500

ttccctatcc tccccggaga gatcttcaag tacaaatgga ccgtcaccgt ggaggacggc     1560

cccacaaagt ccgatccccg gtgcctgacc cggtactatt ccagctttgt caacatggag     1620

cgggacctcg ccagcggcct gatcggccct ctgctcatct gctataagga gtccgtcgat     1680

cagaggggaa accagatcat gtccgataag cggaatgtga tcctgttttc cgtgtttgac     1740

gaaaaccggt cctggtatct gaccgagaac atccagcggt ttctgcctaa ccccgctggc     1800

gtgcaactgg aagatcctga gttccaggct tccaatatca tgcacagcat caacggctac     1860

gtcttcgaca gcctgcagct gtccgtctgc ctgcacgaag tcgcctactg gtacattctc     1920

agcattggcg cccagacaga cttcctgtcc gtctttttct ccggctatac cttcaaacat     1980

aagatggtct acgaggatac cctcacactg ttccctttca gcggcgaaac cgtgtttatg     2040

agcatggaaa atcccggcct gtggatttta ggatgccaca actccgattt caggaatagg     2100

ggcatgacag ctctcctcaa agtgtcctcc tgcgacaaga acacaggcga ctactacgag     2160

gacagctatg aggatatttc cgcctacctg ctcagcaaga ataatgccat cgagcctagg     2220

tccttctccc aaaactcccg gcatcccagc acccggcaga agcagttcaa tgccaccaca     2280

attcctgaaa atagaacaac cctgcagtcc gaccaggagg aaatcgacta cgatgacacc     2340

atctccgtcg agatgaagaa ggaagacttc gacatctatg acgaggacga aaaccagagc     2400

cctcggtcct ttcagaaaaa aacacggcat tactttatcg ctgccgtcga acggctgtgg     2460

gactacggca tgagctcctc cccccatgtg ctccggaatc gggctcaatc cggctccgtg     2520

cctcagttta agaaggtggt gtttcaagag ttcaccgacg gcagctttac acagcccctg     2580

tacaggggag agctgaacga gcacctggga ctgctcggac cttacattcg ggccgaagtc     2640

gaggataaca tcatggtgac ctttaggaat caggcttccc ggccttactc cttctactcc     2700

agcctcatct cctacgaaga agaccaacgg cagggcgccg agcctcggaa gaatttcgtg     2760

aagcccaatg aaaccaaaac atacttttgg aaagtccagc accacatggc ccctaccaag     2820

gatgagttcg actgcaaagc ctgggcctat ttctccgatg tggatctgga gaaggacgtc     2880

cattccggac tgatcggccc cctcctcgtc tgccacacca acaccctcaa tcctgcccac     2940

ggcaggcagg tgacagtcca ggagttcgcc ctgtttttca ccatctttga cgagaccaag     3000

tcctggtact ttaccgagaa tatggaaagg aattgcaggg ccccctgcaa cattcagatg     3060

gaggacccca ccttcaaaga gaactaccgg tttcatgcca ttaatggata catcatggac     3120

acactgcccg gcctggtgat ggctcaggac caacggattc ggtggtacct gctgagcatg     3180

ggctccaacg aaaatatcca cagcatccac tttagcggcc acgtgtttac cgtgcggaag     3240

aaggaggagt ataaaatggc cctctacaac ctctatcccg gcgtgttcga aacagtcgag     3300

atgctcccta gcaaggccgg aatctggagg gtggaatgcc tgattggcga acatctgcac     3360

gccggaatga gcaccctctt cctggtctac agcaacaaat gtcagacccc tctgggcatg     3420

gcttccggcc acatcaggga ctttcagatt accgctagcg gacaatatgg ccagtgggcc     3480

cctaaactcg ctaggctgca ctacagcgga agcatcaacg cctggtccac aaaggaacct     3540

ttctcctgga tcaaggtgga tctcctcgcc cctatgatca tccatggcat caagacccaa     3600

ggcgctaggc agaagtttag ctccctgtac atcagccagt ttatcatcat gtactccctc     3660

gacggcaaga agtggcagac ataccgggga aactccacag gcaccctgat ggtgttcttt     3720

ggcaacgtgg acagcagcgg aattaagcat aatattttca accctcctat catcgccagg     3780

tacatccggc tgcaccctac acactacagc atcaggagca ccctgaggat ggagctgatg     3840

ggctgcgatc tgaatagctg ctccatgccc ctcggcatgg agagcaaggc tatttccgac     3900

gcccaaatta ccgccagctc ctatttcacc aacatgttcg ccacatggag ccctagcaaa     3960

gctcggctcc atctccaggg caggtccaac gcctggcggc ctcaggtgaa taatcccaaa     4020

gaatggctgc aggtcgactt ccagaagaca atgaaagtga ccggcgtgac cacccaggga     4080

gtcaaaagcc tcctcaccag catgtacgtc aaagagttcc tgatcagctc ctcccaggac     4140

ggacatcaat ggacactctt ttttcagaac ggcaaggtga aggtgttcca gggcaaccag     4200

gattccttta cccctgtggt caactcctta gatcctcccc tcctgacacg gtacctgcgg     4260

attcaccctc agtcctgggt gcatcagatc gctctgagga tggaagtgct cggctgcgaa     4320

gcccaagacc tgtacggatc cggtggcggt ggctccggtg gaggcggaag cggcggtgga     4380

ggatcaggcg gtggaggtag cggcggaggc ggtagctcca gctctagtaa agctccccct     4440

ccttccctgc cctcaccctc aagactgcct ggaccttccg acactcccat cctgccacag     4500

gtggagtgcc ctccatgtcc agcaccccct gtcgcaggtc catctgtgtt cctgtttcca     4560

cccaagccta aagaccagct gatgatctcc cgcaccccag aagtcacctg tgtggtcgtg     4620

gatgtgagcc atgaagaccc cgaggtccag ttcaattggt acgtggatgg cgtcgaggtg     4680

cacaacgcta agacaaaacc tagagaagag cagttcaact ctacctttcg cgtcgtgagt     4740

gtgctgacag tcgtgcacca ggactggctg aatggcaagg agtataagtg caaagtgagc     4800

aacaaaggac tgcctgcctc aatcgaaaag actatttcca agaccaaagg acagccaaga     4860

gagccccagg tgtacaccct gcctccaagc cgcgaagaga tgactaaaaa tcaggtctct     4920

ctgacctgtc tggtgaaggg gttttatcct agtgatatcg ccgtggaatg ggagtcaaac     4980

ggtcagccag agaacaatta caagaccaca ccccctatgc tggacagcga tgggtctttc     5040

tttctgtata gcaaactgac agtggacaag tctcggtggc agcagggtaa cgtcttctct     5100

tgcagtgtgc tgcacgaagc actgcacaat cattacaccc agaagtcact gtcactgagc     5160

ccaggaaaa                                                             5169


<210>  11
<211>  1716
<212>  PRT
<213>  DS-F8ںϵװ

<400>  11

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 Phe 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 Gly Ser  Gly Gly Gly 
    1430                 1435                 1440             


Gly Ser  Gly Gly Gly Gly Ser  Gly Gly Gly Gly Ser  Gly Gly Gly 
    1445                 1450                 1455             


Gly Ser  Gly Gly Gly Gly Ser  Ser Ser Ser Ser Lys  Ala Pro Pro 
    1460                 1465                 1470             


Pro Ser  Leu Pro Ser Pro Ser  Arg Leu Pro Gly Pro  Ser Asp Thr 
    1475                 1480                 1485             


Pro Ile  Leu Pro Gln Val Glu  Cys Pro Pro Cys Pro  Ala Pro Pro 
    1490                 1495                 1500             


Val Ala  Gly Pro Ser Val Phe  Leu Phe Pro Pro Lys  Pro Lys Asp 
    1505                 1510                 1515             


Gln Leu  Met Ile Ser Arg Thr  Pro Glu Val Thr Cys  Val Val Val 
    1520                 1525                 1530             


Asp Val  Ser His Glu Asp Pro  Glu Val Gln Phe Asn  Trp Tyr Val 
    1535                 1540                 1545             


Asp Gly  Val Glu Val His Asn  Ala Lys Thr Lys Pro  Arg Glu Glu 
    1550                 1555                 1560             


Gln Phe  Asn Ser Thr Phe Arg  Val Val Ser Val Leu  Thr Val Val 
    1565                 1570                 1575             


His Gln  Asp Trp Leu Asn Gly  Lys Glu Tyr Lys Cys  Lys Val Ser 
    1580                 1585                 1590             


Asn Lys  Gly Leu Pro Ala Ser  Ile Glu Lys Thr Ile  Ser Lys Thr 
    1595                 1600                 1605             


Lys Gly  Gln Pro Arg Glu Pro  Gln Val Tyr Thr Leu  Pro Pro Ser 
    1610                 1615                 1620             


Arg Glu  Glu Met Thr Lys Asn  Gln Val Ser Leu Thr  Cys Leu Val 
    1625                 1630                 1635             


Lys Gly  Phe Tyr Pro Ser Asp  Ile Ala Val Glu Trp  Glu Ser Asn 
    1640                 1645                 1650             


Gly Gln  Pro Glu Asn Asn Tyr  Lys Thr Thr Pro Pro  Met Leu Asp 
    1655                 1660                 1665             


Ser Asp  Gly Ser Phe Phe Leu  Tyr Ser Lys Leu Thr  Val Asp Lys 
    1670                 1675                 1680             


Ser Arg  Trp Gln Gln Gly Asn  Val Phe Ser Cys Ser  Val Leu His 
    1685                 1690                 1695             


Glu Ala  Leu His Asn His Tyr  Thr Gln Lys Ser Leu  Ser Leu Ser 
    1700                 1705                 1710             


Pro Gly  Lys 
    1715     


