                         SEQUENCE LISTING

<110>  Genentech, Inc.
       LI, Kang
       FUNG, Sek Chung
       YAO, Zhengbin
 
<120>  NOVEL ANTI-NOTCH3 ANTIBODIES AND THEIR USE IN THE DETECTION AND 
       DIAGNOSIS OF DISEASE

<130>  P4023R1 WO

<150>  US  60/852861
<151>  2006-10-19

<160>  25    

<170>  PatentIn version 3.3

<210>  1
<211>  2321
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Gly Pro Gly Ala Arg Gly Arg Arg Arg Arg Arg Arg Pro Met Ser 
1               5                   10                  15      


Pro Pro Pro Pro Pro Pro Pro Val Arg Ala Leu Pro Leu Leu Leu Leu 
            20                  25                  30          


Leu Ala Gly Pro Gly Ala Ala Ala Pro Pro Cys Leu Asp Gly Ser Pro 
        35                  40                  45              


Cys Ala Asn Gly Gly Arg Cys Thr Gln Leu Pro Ser Arg Glu Ala Ala 
    50                  55                  60                  


Cys Leu Cys Pro Pro Gly Trp Val Gly Glu Arg Cys Gln Leu Glu Asp 
65                  70                  75                  80  


Pro Cys His Ser Gly Pro Cys Ala Gly Arg Gly Val Cys Gln Ser Ser 
                85                  90                  95      


Val Val Ala Gly Thr Ala Arg Phe Ser Cys Arg Cys Pro Arg Gly Phe 
            100                 105                 110         


Arg Gly Pro Asp Cys Ser Leu Pro Asp Pro Cys Leu Ser Ser Pro Cys 
        115                 120                 125             


Ala His Gly Ala Arg Cys Ser Val Gly Pro Asp Gly Arg Phe Leu Cys 
    130                 135                 140                 


Ser Cys Pro Pro Gly Tyr Gln Gly Arg Ser Cys Arg Ser Asp Val Asp 
145                 150                 155                 160 


Glu Cys Arg Val Gly Glu Pro Cys Arg His Gly Gly Thr Cys Leu Asn 
                165                 170                 175     


Thr Pro Gly Ser Phe Arg Cys Gln Cys Pro Ala Gly Tyr Thr Gly Pro 
            180                 185                 190         


Leu Cys Glu Asn Pro Ala Val Pro Cys Ala Pro Ser Pro Cys Arg Asn 
        195                 200                 205             


Gly Gly Thr Cys Arg Gln Ser Gly Asp Leu Thr Tyr Asp Cys Ala Cys 
    210                 215                 220                 


Leu Pro Gly Phe Glu Gly Gln Asn Cys Glu Val Asn Val Asp Asp Cys 
225                 230                 235                 240 


Pro Gly His Arg Cys Leu Asn Gly Gly Thr Cys Val Asp Gly Val Asn 
                245                 250                 255     


Thr Tyr Asn Cys Gln Cys Pro Pro Glu Trp Thr Gly Gln Phe Cys Thr 
            260                 265                 270         


Glu Asp Val Asp Glu Cys Gln Leu Gln Pro Asn Ala Cys His Asn Gly 
        275                 280                 285             


Gly Thr Cys Phe Asn Thr Leu Gly Gly His Ser Cys Val Cys Val Asn 
    290                 295                 300                 


Gly Trp Thr Gly Glu Ser Cys Ser Gln Asn Ile Asp Asp Cys Ala Thr 
305                 310                 315                 320 


Ala Val Cys Phe His Gly Ala Thr Cys His Asp Arg Val Ala Ser Phe 
                325                 330                 335     


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


Asp Ala Cys Val Ser Asn Pro Cys His Glu Asp Ala Ile Cys Asp Thr 
        355                 360                 365             


Asn Pro Val Asn Gly Arg Ala Ile Cys Thr Cys Pro Pro Gly Phe Thr 
    370                 375                 380                 


Gly Gly Ala Cys Asp Gln Asp Val Asp Glu Cys Ser Ile Gly Ala Asn 
385                 390                 395                 400 


Pro Cys Glu His Leu Gly Arg Cys Val Asn Thr Gln Gly Ser Phe Leu 
                405                 410                 415     


Cys Gln Cys Gly Arg Gly Tyr Thr Gly Pro Arg Cys Glu Thr Asp Val 
            420                 425                 430         


Asn Glu Cys Leu Ser Gly Pro Cys Arg Asn Gln Ala Thr Cys Leu Asp 
        435                 440                 445             


Arg Ile Gly Gln Phe Thr Cys Ile Cys Met Ala Gly Phe Thr Gly Thr 
    450                 455                 460                 


Tyr Cys Glu Val Asp Ile Asp Glu Cys Gln Ser Ser Pro Cys Val Asn 
465                 470                 475                 480 


Gly Gly Val Cys Lys Asp Arg Val Asn Gly Phe Ser Cys Thr Cys Pro 
                485                 490                 495     


Ser Gly Phe Ser Gly Ser Thr Cys Gln Leu Asp Val Asp Glu Cys Ala 
            500                 505                 510         


Ser Thr Pro Cys Arg Asn Gly Ala Lys Cys Val Asp Gln Pro Asp Gly 
        515                 520                 525             


Tyr Glu Cys Arg Cys Ala Glu Gly Phe Glu Gly Thr Leu Cys Asp Arg 
    530                 535                 540                 


Asn Val Asp Asp Cys Ser Pro Asp Pro Cys His His Gly Arg Cys Val 
545                 550                 555                 560 


Asp Gly Ile Ala Ser Phe Ser Cys Ala Cys Ala Pro Gly Tyr Thr Gly 
                565                 570                 575     


Thr Arg Cys Glu Ser Gln Val Asp Glu Cys Arg Ser Gln Pro Cys Arg 
            580                 585                 590         


His Gly Gly Lys Cys Leu Asp Leu Val Asp Lys Tyr Leu Cys Arg Cys 
        595                 600                 605             


Pro Ser Gly Thr Thr Gly Val Asn Cys Glu Val Asn Ile Asp Asp Cys 
    610                 615                 620                 


Ala Ser Asn Pro Cys Thr Phe Gly Val Cys Arg Asp Gly Ile Asn Arg 
625                 630                 635                 640 


Tyr Asp Cys Val Cys Gln Pro Gly Phe Thr Gly Pro Leu Cys Asn Val 
                645                 650                 655     


Glu Ile Asn Glu Cys Ala Ser Ser Pro Cys Gly Glu Gly Gly Ser Cys 
            660                 665                 670         


Val Asp Gly Glu Asn Gly Phe Arg Cys Leu Cys Pro Pro Gly Ser Leu 
        675                 680                 685             


Pro Pro Leu Cys Leu Pro Pro Ser His Pro Cys Ala His Glu Pro Cys 
    690                 695                 700                 


Ser His Gly Ile Cys Tyr Asp Ala Pro Gly Gly Phe Arg Cys Val Cys 
705                 710                 715                 720 


Glu Pro Gly Trp Ser Gly Pro Arg Cys Ser Gln Ser Leu Ala Arg Asp 
                725                 730                 735     


Ala Cys Glu Ser Gln Pro Cys Arg Ala Gly Gly Thr Cys Ser Ser Asp 
            740                 745                 750         


Gly Met Gly Phe His Cys Thr Cys Pro Pro Gly Val Gln Gly Arg Gln 
        755                 760                 765             


Cys Glu Leu Leu Ser Pro Cys Thr Pro Asn Pro Cys Glu His Gly Gly 
    770                 775                 780                 


Arg Cys Glu Ser Ala Pro Gly Gln Leu Pro Val Cys Ser Cys Pro Gln 
785                 790                 795                 800 


Gly Trp Gln Gly Pro Arg Cys Gln Gln Asp Val Asp Glu Cys Ala Gly 
                805                 810                 815     


Pro Ala Pro Cys Gly Pro His Gly Ile Cys Thr Asn Leu Ala Gly Ser 
            820                 825                 830         


Phe Ser Cys Thr Cys His Gly Gly Tyr Thr Gly Pro Ser Cys Asp Gln 
        835                 840                 845             


Asp Ile Asn Asp Cys Asp Pro Asn Pro Cys Leu Asn Gly Gly Ser Cys 
    850                 855                 860                 


Gln Asp Gly Val Gly Ser Phe Ser Cys Ser Cys Leu Pro Gly Phe Ala 
865                 870                 875                 880 


Gly Pro Arg Cys Ala Arg Asp Val Asp Glu Cys Leu Ser Asn Pro Cys 
                885                 890                 895     


Gly Pro Gly Thr Cys Thr Asp His Val Ala Ser Phe Thr Cys Thr Cys 
            900                 905                 910         


Pro Pro Gly Tyr Gly Gly Phe His Cys Glu Gln Asp Leu Pro Asp Cys 
        915                 920                 925             


Ser Pro Ser Ser Cys Phe Asn Gly Gly Thr Cys Val Asp Gly Val Asn 
    930                 935                 940                 


Ser Phe Ser Cys Leu Cys Arg Pro Gly Tyr Thr Gly Ala His Cys Gln 
945                 950                 955                 960 


His Glu Ala Asp Pro Cys Leu Ser Arg Pro Cys Leu His Gly Gly Val 
                965                 970                 975     


Cys Ser Ala Ala His Pro Gly Phe Arg Cys Thr Cys Leu Glu Ser Phe 
            980                 985                 990         


Thr Gly Pro Gln Cys Gln Thr Leu  Val Asp Trp Cys Ser  Arg Gln Pro 
        995                 1000                 1005             


Cys Gln  Asn Gly Gly Arg Cys  Val Gln Thr Gly Ala  Tyr Cys Leu 
    1010                 1015                 1020             


Cys Pro  Pro Gly Trp Ser Gly  Arg Leu Cys Asp Ile  Arg Ser Leu 
    1025                 1030                 1035             


Pro Cys  Arg Glu Ala Ala Ala  Gln Ile Gly Val Arg  Leu Glu Gln 
    1040                 1045                 1050             


Leu Cys  Gln Ala Gly Gly Gln  Cys Val Asp Glu Asp  Ser Ser His 
    1055                 1060                 1065             


Tyr Cys  Val Cys Pro Glu Gly  Arg Thr Gly Ser His  Cys Glu Gln 
    1070                 1075                 1080             


Glu Val  Asp Pro Cys Leu Ala  Gln Pro Cys Gln His  Gly Gly Thr 
    1085                 1090                 1095             


Cys Arg  Gly Tyr Met Gly Gly  Tyr Met Cys Glu Cys  Leu Pro Gly 
    1100                 1105                 1110             


Tyr Asn  Gly Asp Asn Cys Glu  Asp Asp Val Asp Glu  Cys Ala Ser 
    1115                 1120                 1125             


Gln Pro  Cys Gln His Gly Gly  Ser Cys Ile Asp Leu  Val Ala Arg 
    1130                 1135                 1140             


Tyr Leu  Cys Ser Cys Pro Pro  Gly Thr Leu Gly Val  Leu Cys Glu 
    1145                 1150                 1155             


Ile Asn  Glu Asp Asp Cys Gly  Pro Gly Pro Pro Leu  Asp Ser Gly 
    1160                 1165                 1170             


Pro Arg  Cys Leu His Asn Gly  Thr Cys Val Asp Leu  Val Gly Gly 
    1175                 1180                 1185             


Phe Arg  Cys Thr Cys Pro Pro  Gly Tyr Thr Gly Leu  Arg Cys Glu 
    1190                 1195                 1200             


Ala Asp  Ile Asn Glu Cys Arg  Ser Gly Ala Cys His  Ala Ala His 
    1205                 1210                 1215             


Thr Arg  Asp Cys Leu Gln Asp  Pro Gly Gly Gly Phe  Arg Cys Leu 
    1220                 1225                 1230             


Cys His  Ala Gly Phe Ser Gly  Pro Arg Cys Gln Thr  Val Leu Ser 
    1235                 1240                 1245             


Pro Cys  Glu Ser Gln Pro Cys  Gln His Gly Gly Gln  Cys Arg Pro 
    1250                 1255                 1260             


Ser Pro  Gly Pro Gly Gly Gly  Leu Thr Phe Thr Cys  His Cys Ala 
    1265                 1270                 1275             


Gln Pro  Phe Trp Gly Pro Arg  Cys Glu Arg Val Ala  Arg Ser Cys 
    1280                 1285                 1290             


Arg Glu  Leu Gln Cys Pro Val  Gly Val Pro Cys Gln  Gln Thr Pro 
    1295                 1300                 1305             


Arg Gly  Pro Arg Cys Ala Cys  Pro Pro Gly Leu Ser  Gly Pro Ser 
    1310                 1315                 1320             


Cys Arg  Ser Phe Pro Gly Ser  Pro Pro Gly Ala Ser  Asn Ala Ser 
    1325                 1330                 1335             


Cys Ala  Ala Ala Pro Cys Leu  His Gly Gly Ser Cys  Arg Pro Ala 
    1340                 1345                 1350             


Pro Leu  Ala Pro Phe Phe Arg  Cys Ala Cys Ala Gln  Gly Trp Thr 
    1355                 1360                 1365             


Gly Pro  Arg Cys Glu Ala Pro  Ala Ala Ala Pro Glu  Val Ser Glu 
    1370                 1375                 1380             


Glu Pro  Arg Cys Pro Arg Ala  Ala Cys Gln Ala Lys  Arg Gly Asp 
    1385                 1390                 1395             


Gln Arg  Cys Asp Arg Glu Cys  Asn Ser Pro Gly Cys  Gly Trp Asp 
    1400                 1405                 1410             


Gly Gly  Asp Cys Ser Leu Ser  Val Gly Asp Pro Trp  Arg Gln Cys 
    1415                 1420                 1425             


Glu Ala  Leu Gln Cys Trp Arg  Leu Phe Asn Asn Ser  Arg Cys Asp 
    1430                 1435                 1440             


Pro Ala  Cys Ser Ser Pro Ala  Cys Leu Tyr Asp Asn  Phe Asp Cys 
    1445                 1450                 1455             


His Ala  Gly Gly Arg Glu Arg  Thr Cys Asn Pro Val  Tyr Glu Lys 
    1460                 1465                 1470             


Tyr Cys  Ala Asp His Phe Ala  Asp Gly Arg Cys Asp  Gln Gly Cys 
    1475                 1480                 1485             


Asn Thr  Glu Glu Cys Gly Trp  Asp Gly Leu Asp Cys  Ala Ser Glu 
    1490                 1495                 1500             


Val Pro  Ala Leu Leu Ala Arg  Gly Val Leu Val Leu  Thr Val Leu 
    1505                 1510                 1515             


Leu Pro  Pro Glu Glu Leu Leu  Arg Ser Ser Ala Asp  Phe Leu Gln 
    1520                 1525                 1530             


Arg Leu  Ser Ala Ile Leu Arg  Thr Ser Leu Arg Phe  Arg Leu Asp 
    1535                 1540                 1545             


Ala His  Gly Gln Ala Met Val  Phe Pro Tyr His Arg  Pro Ser Pro 
    1550                 1555                 1560             


Gly Ser  Glu Pro Arg Ala Arg  Arg Glu Leu Ala Pro  Glu Val Ile 
    1565                 1570                 1575             


Gly Ser  Val Val Met Leu Glu  Ile Asp Asn Arg Leu  Cys Leu Gln 
    1580                 1585                 1590             


Ser Pro  Glu Asn Asp His Cys  Phe Pro Asp Ala Gln  Ser Ala Ala 
    1595                 1600                 1605             


Asp Tyr  Leu Gly Ala Leu Ser  Ala Val Glu Arg Leu  Asp Phe Pro 
    1610                 1615                 1620             


Tyr Pro  Leu Arg Asp Val Arg  Gly Glu Pro Leu Glu  Pro Pro Glu 
    1625                 1630                 1635             


Pro Ser  Val Pro Leu Leu Pro  Leu Leu Val Ala Gly  Ala Val Leu 
    1640                 1645                 1650             


Leu Leu  Val Ile Leu Val Leu  Gly Val Met Val Ala  Arg Arg Lys 
    1655                 1660                 1665             


Arg Glu  His Ser Thr Leu Trp  Phe Pro Glu Gly Phe  Ser Leu His 
    1670                 1675                 1680             


Lys Asp  Val Ala Ser Gly His  Lys Gly Arg Arg Glu  Pro Val Gly 
    1685                 1690                 1695             


Gln Asp  Ala Leu Gly Met Lys  Asn Met Ala Lys Gly  Glu Ser Leu 
    1700                 1705                 1710             


Met Gly  Glu Val Ala Thr Asp  Trp Met Asp Thr Glu  Cys Pro Glu 
    1715                 1720                 1725             


Ala Lys  Arg Leu Lys Val Glu  Glu Pro Gly Met Gly  Ala Glu Glu 
    1730                 1735                 1740             


Ala Val  Asp Cys Arg Gln Trp  Thr Gln His His Leu  Val Ala Ala 
    1745                 1750                 1755             


Asp Ile  Arg Val Ala Pro Ala  Met Ala Leu Thr Pro  Pro Gln Gly 
    1760                 1765                 1770             


Asp Ala  Asp Ala Asp Gly Met  Asp Val Asn Val Arg  Gly Pro Asp 
    1775                 1780                 1785             


Gly Phe  Thr Pro Leu Met Leu  Ala Ser Phe Cys Gly  Gly Ala Leu 
    1790                 1795                 1800             


Glu Pro  Met Pro Thr Glu Glu  Asp Glu Ala Asp Asp  Thr Ser Ala 
    1805                 1810                 1815             


Ser Ile  Ile Ser Asp Leu Ile  Cys Gln Gly Ala Gln  Leu Gly Ala 
    1820                 1825                 1830             


Arg Thr  Asp Arg Thr Gly Glu  Thr Ala Leu His Leu  Ala Ala Arg 
    1835                 1840                 1845             


Tyr Ala  Arg Ala Asp Ala Ala  Lys Arg Leu Leu Asp  Ala Gly Ala 
    1850                 1855                 1860             


Asp Thr  Asn Ala Gln Asp His  Ser Gly Arg Thr Pro  Leu His Thr 
    1865                 1870                 1875             


Ala Val  Thr Ala Asp Ala Gln  Gly Val Phe Gln Ile  Leu Ile Arg 
    1880                 1885                 1890             


Asn Arg  Ser Thr Asp Leu Asp  Ala Arg Met Ala Asp  Gly Ser Thr 
    1895                 1900                 1905             


Ala Leu  Ile Leu Ala Ala Arg  Leu Ala Val Glu Gly  Met Val Glu 
    1910                 1915                 1920             


Glu Leu  Ile Ala Ser His Ala  Asp Val Asn Ala Val  Asp Glu Leu 
    1925                 1930                 1935             


Gly Lys  Ser Ala Leu His Trp  Ala Ala Ala Val Asn  Asn Val Glu 
    1940                 1945                 1950             


Ala Thr  Leu Ala Leu Leu Lys  Asn Gly Ala Asn Lys  Asp Met Gln 
    1955                 1960                 1965             


Asp Ser  Lys Glu Glu Thr Pro  Leu Phe Leu Ala Ala  Arg Glu Gly 
    1970                 1975                 1980             


Ser Tyr  Glu Ala Ala Lys Leu  Leu Leu Asp His Phe  Ala Asn Arg 
    1985                 1990                 1995             


Glu Ile  Thr Asp His Leu Asp  Arg Leu Pro Arg Asp  Val Ala Gln 
    2000                 2005                 2010             


Glu Arg  Leu His Gln Asp Ile  Val Arg Leu Leu Asp  Gln Pro Ser 
    2015                 2020                 2025             


Gly Pro  Arg Ser Pro Pro Gly  Pro His Gly Leu Gly  Pro Leu Leu 
    2030                 2035                 2040             


Cys Pro  Pro Gly Ala Phe Leu  Pro Gly Leu Lys Ala  Ala Gln Ser 
    2045                 2050                 2055             


Gly Ser  Lys Lys Ser Arg Arg  Pro Pro Gly Lys Ala  Gly Leu Gly 
    2060                 2065                 2070             


Pro Gln  Gly Pro Arg Gly Arg  Gly Lys Lys Leu Thr  Leu Ala Cys 
    2075                 2080                 2085             


Pro Gly  Pro Leu Ala Asp Ser  Ser Val Thr Leu Ser  Pro Val Asp 
    2090                 2095                 2100             


Ser Leu  Asp Ser Pro Arg Pro  Phe Gly Gly Pro Pro  Ala Ser Pro 
    2105                 2110                 2115             


Gly Gly  Phe Pro Leu Glu Gly  Pro Tyr Ala Ala Ala  Thr Ala Thr 
    2120                 2125                 2130             


Ala Val  Ser Leu Ala Gln Leu  Gly Gly Pro Gly Arg  Ala Gly Leu 
    2135                 2140                 2145             


Gly Arg  Gln Pro Pro Gly Gly  Cys Val Leu Ser Leu  Gly Leu Leu 
    2150                 2155                 2160             


Asn Pro  Val Ala Val Pro Leu  Asp Trp Ala Arg Leu  Pro Pro Pro 
    2165                 2170                 2175             


Ala Pro  Pro Gly Pro Ser Phe  Leu Leu Pro Leu Ala  Pro Gly Pro 
    2180                 2185                 2190             


Gln Leu  Leu Asn Pro Gly Thr  Pro Val Ser Pro Gln  Glu Arg Pro 
    2195                 2200                 2205             


Pro Pro  Tyr Leu Ala Val Pro  Gly His Gly Glu Glu  Tyr Pro Val 
    2210                 2215                 2220             


Ala Gly  Ala His Ser Ser Pro  Pro Lys Ala Arg Phe  Leu Arg Val 
    2225                 2230                 2235             


Pro Ser  Glu His Pro Tyr Leu  Thr Pro Ser Pro Glu  Ser Pro Glu 
    2240                 2245                 2250             


His Trp  Ala Ser Pro Ser Pro  Pro Ser Leu Ser Asp  Trp Ser Glu 
    2255                 2260                 2265             


Ser Thr  Pro Ser Pro Ala Thr  Ala Thr Gly Ala Met  Ala Thr Thr 
    2270                 2275                 2280             


Thr Gly  Ala Leu Pro Ala Gln  Pro Leu Pro Leu Ser  Val Pro Ser 
    2285                 2290                 2295             


Ser Leu  Ala Gln Ala Gln Thr  Gln Leu Gly Pro Gln  Pro Glu Val 
    2300                 2305                 2310             


Thr Pro  Lys Arg Gln Val Leu  Ala 
    2315                 2320     


<210>  2
<211>  123
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region derived from mAb 255A-71

<400>  2

Ser Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 
1               5                   10                  15      


Gln Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser 
            20                  25                  30          


Gly Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu 
        35                  40                  45              


Trp Met Gly Phe Ile Ser Tyr Asp Gly Ser Asn Asn Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  


Phe Leu Lys Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Phe Tyr 
                85                  90                  95      


Cys Ala Thr Leu Tyr Tyr Asp Tyr Asp Gly Asn Tyr Phe Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala 
        115                 120             


<210>  3
<211>  116
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region derived from mAb 255A-71

<400>  3

Cys Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu 
1               5                   10                  15      


Gly Asp Arg Val Thr Ile Ser Cys Arg Thr Ser Gln Asp Ile Ser Asn 
            20                  25                  30          


Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu 
        35                  40                  45              


Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu 
65                  70                  75                  80  


Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Ala Leu Pro 
                85                  90                  95      


Leu Thr Phe Gly Pro Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala 
            100                 105                 110         


Ala Pro Thr Val 
        115     


<210>  4
<211>  120
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region derived from mAb 255A-77

<400>  4

Cys Gln Val Gln Leu Gln Gln Ser Gly Asp Asp Leu Val Lys Pro Gly 
1               5                   10                  15      


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


Tyr Trp Ile Asn Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp 
        35                  40                  45              


Ile Gly His Ile Gly Pro Gly Ser Gly Ser Thr Tyr Tyr Asn Glu Ile 
    50                  55                  60                  


Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala 
65                  70                  75                  80  


Tyr Ile Gln Leu Ser Ser Leu Ser Ser Glu Asp Ser Ala Val Tyr Phe 
                85                  90                  95      


Cys Val Leu Thr Arg Tyr Phe Tyr Ala Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Ser Val Thr Val Ser Ser Ala 
        115                 120 


<210>  5
<211>  123
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region derived from 255A-77

<400>  5

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ala Val Thr Ala Gly 
1               5                   10                  15      


Glu Lys Val Thr Met Arg Cys Lys Ser Ser Gln Ser Leu Leu Trp Ser 
            20                  25                  30          


Val Asn Gln Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys Gln Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Ile Arg Glu Ser Trp Val 
    50                  55                  60                  


Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Asn Val His Val Glu Asp Leu Ala Val Tyr Tyr Cys Gln His 
                85                  90                  95      


Asn His Gly Ser Phe Leu Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu 
            100                 105                 110         


Glu Leu Lys Arg Ala Asp Ala Ala Pro Thr Val 
        115                 120             


<210>  6
<211>  121
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain variable region derived from 256A-13

<400>  6

Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys Pro Gly 
1               5                   10                  15      


Thr Ser Val Lys Met Ala Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr 
            20                  25                  30          


His Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp 
        35                  40                  45              


Ile Gly Thr Ile Asn Pro Ser Asn Asp Phe Thr Asp Cys Asn Gln Lys 
    50                  55                  60                  


Phe Lys Asp Lys Ala Ile Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala 
65                  70                  75                  80  


Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr 
                85                  90                  95      


Cys Ala Ser Gly Leu Thr Ala Arg Ala Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ala Ala 
        115                 120     


<210>  7
<211>  102
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain variable region derived from 256A-13

<400>  7

Arg Ala Thr Ile Ser Cys Arg Ala Ser Gln Ser Val Thr Thr Ser Asn 
1               5                   10                  15      


Tyr Ser Tyr Met His Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro Lys 
            20                  25                  30          


Leu Leu Ile Lys Tyr Ala Ser Asn Leu Asp Ser Gly Val Pro Ala Arg 
        35                  40                  45              


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His Pro 
    50                  55                  60                  


Val Glu Glu Glu Asp Thr Ala Thr Phe Tyr Cys Gln His Ser Trp Glu 
65                  70                  75                  80  


Ile Pro Tyr Thr Phe Gly Gly Gly Thr Asn Leu Glu Ile Lys Arg Ala 
                85                  90                  95      


Asp Ala Ala Pro Thr Val 
            100         


<210>  8
<211>  12
<212>  PRT
<213>  Artificial 

<220>
<223>  CDR-H1 derived from the heavy chain variable region of mAb 
       255A-71

<400>  8

Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr Trp Asn Trp 
1               5                   10          


<210>  9
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H2 derived from the heavy chain variable region of mAb 
       255A-71

<400>  9

Ile Ser Tyr Asp Gly Ser Asn Asn Tyr Asn 
1               5                   10  


<210>  10
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H3 derived from the heavy chain variable region of mAb 
       255A-71

<400>  10

Leu Tyr Tyr Asp Tyr Asp Gly Asn Tyr Phe Asp Tyr 
1               5                   10          


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

<220>
<223>  CDR-L1 derived from the heavy chain variable region of mAb 
       255A-71

<400>  11

Arg Thr Ser Gln Asp Ile Ser Asn Tyr Leu Asn 
1               5                   10      


<210>  12
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L2 derived from the heavy chain variable region of mAb 
       255A-71

<400>  12

Tyr Thr Ser Arg Leu His Ser 
1               5           


<210>  13
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L3 derived from the heavy chain variable region of mAb 
       255A-71

<400>  13

Gln Gln Gly Asn Ala Leu Pro Thr 
1               5               


<210>  14
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H1 derived from the heavy chain variable region of mAb 
       255A-77

<400>  14

Gly Tyr Thr Phe Thr Ser Tyr Trp Ile Asn 
1               5                   10  


<210>  15
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H2 derived from the heavy chain variable region of mAb 
       255A-77

<400>  15

His Ile Gly Pro Gly Ser Gly Ser Thr Tyr Tyr Asn 
1               5                   10          


<210>  16
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H3 derived from the heavy chain variable region of mAb 
       255A-77

<400>  16

Thr Arg Tyr Phe Tyr Ala Met Asp Tyr 
1               5                   


<210>  17
<211>  17
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L1 derived from the heavy chain variable region of mAb 
       255A-77

<400>  17

Lys Ser Ser Gln Ser Leu Leu Trp Ser Val Asn Gln Asn Asn Tyr Leu 
1               5                   10                  15      


Ser 
    


<210>  18
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L2 derived from the heavy chain variable region of mAb 
       255A-77

<400>  18

Gly Ala Ser Ile Arg Glu Ser 
1               5           


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

<220>
<223>  CDR-L3 derived from the heavy chain variable region of mAb 
       255A-77

<400>  19

Gln His Asn His Gly Ser Phe Leu Pro Leu Thr 
1               5                   10      


<210>  20
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H1 derived from the heavy chain varible region of mAb 256A-13

<400>  20

Gly Tyr Thr Phe Thr Thr His Trp Met Asn Trp 
1               5                   10      


<210>  21
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H2 derived from the heavy chain varible region of mAb 256A-13

<400>  21

Ile Asn Pro Ser Asn Asp Phe Thr Asp Cys Asn 
1               5                   10      


<210>  22
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-H3 derived from the heavy chain varible region of mAb 256A-13

<400>  22

Thr Ala Arg Ala Trp Phe Ala Tyr 
1               5               


<210>  23
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L1 derived from the heavy chain varible region of mAb 256A-13

<400>  23

Arg Ala Ser Gln Ser Val Thr Thr Ser Asn Tyr Ser Tyr Met His 
1               5                   10                  15  


<210>  24
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L2 derived from the heavy chain varible region of mAb 256A-13

<400>  24

Tyr Ala Ser Asn Leu Asp Ser Gly 
1               5               


<210>  25
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  CDR-L3 derived from the heavy chain varible region of mAb 256A-13

<400>  25

Gln His Ser Trp Glu Ile Pro Tyr Thr 
1               5                   


