                         SEQUENCE LISTING

<110>  UCL Business plc
       St. Jude Children's Research Hospital
 
<120>  Factor VIII Sequences

<130>  P528068PCT

<150>  GB1210357.8
<151>  2012-06-12

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  51
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Portion of modified Factor VIII B domain sequence

<400>  1
gccactaatg tgtctaacaa cagcaacacc agcaatgaca gcaatgtgtc t                51


<210>  2
<211>  93
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII B domain sequence

<400>  2
agcttcagcc agaatgccac taatgtgtct aacaacagca acaccagcaa tgacagcaat       60

gtgtctcccc cagtgctgaa gaggcaccag agg                                    93


<210>  3
<211>  4425
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII sequence

<400>  3
atgcagattg agctgagcac ctgcttcttc ctgtgcctgc tgaggttctg cttctctgcc       60

accaggagat actacctggg ggctgtggag ctgagctggg actacatgca gtctgacctg      120

ggggagctgc ctgtggatgc caggttcccc cccagagtgc ccaagagctt ccccttcaac      180

acctctgtgg tgtacaagaa gaccctgttt gtggagttca ctgaccacct gttcaacatt      240

gccaagccca ggcccccctg gatgggcctg ctgggcccca ccatccaggc tgaggtgtat      300

gacactgtgg tgatcaccct gaagaacatg gccagccacc ctgtgagcct gcatgctgtg      360

ggggtgagct actggaaggc ctctgagggg gctgagtatg atgaccagac cagccagagg      420

gagaaggagg atgacaaggt gttccctggg ggcagccaca cctatgtgtg gcaggtgctg      480

aaggagaatg gccccatggc ctctgacccc ctgtgcctga cctacagcta cctgagccat      540

gtggacctgg tgaaggacct gaactctggc ctgattgggg ccctgctggt gtgcagggag      600

ggcagcctgg ccaaggagaa gacccagacc ctgcacaagt tcatcctgct gtttgctgtg      660

tttgatgagg gcaagagctg gcactctgaa accaagaaca gcctgatgca ggacagggat      720

gctgcctctg ccagggcctg gcccaagatg cacactgtga atggctatgt gaacaggagc      780

ctgcctggcc tgattggctg ccacaggaag tctgtgtact ggcatgtgat tggcatgggc      840

accacccctg aggtgcacag catcttcctg gagggccaca ccttcctggt caggaaccac      900

aggcaggcca gcctggagat cagccccatc accttcctga ctgcccagac cctgctgatg      960

gacctgggcc agttcctgct gttctgccac atcagcagcc accagcatga tggcatggag     1020

gcctatgtga aggtggacag ctgccctgag gagccccagc tgaggatgaa gaacaatgag     1080

gaggctgagg actatgatga tgacctgact gactctgaga tggatgtggt gaggtttgat     1140

gatgacaaca gccccagctt catccagatc aggtctgtgg ccaagaagca ccccaagacc     1200

tgggtgcact acattgctgc tgaggaggag gactgggact atgcccccct ggtgctggcc     1260

cctgatgaca ggagctacaa gagccagtac ctgaacaatg gcccccagag gattggcagg     1320

aagtacaaga aggtcaggtt catggcctac actgatgaaa ccttcaagac cagggaggcc     1380

atccagcatg agtctggcat cctgggcccc ctgctgtatg gggaggtggg ggacaccctg     1440

ctgatcatct tcaagaacca ggccagcagg ccctacaaca tctaccccca tggcatcact     1500

gatgtgaggc ccctgtacag caggaggctg cccaaggggg tgaagcacct gaaggacttc     1560

cccatcctgc ctggggagat cttcaagtac aagtggactg tgactgtgga ggatggcccc     1620

accaagtctg accccaggtg cctgaccaga tactacagca gctttgtgaa catggagagg     1680

gacctggcct ctggcctgat tggccccctg ctgatctgct acaaggagtc tgtggaccag     1740

aggggcaacc agatcatgtc tgacaagagg aatgtgatcc tgttctctgt gtttgatgag     1800

aacaggagct ggtacctgac tgagaacatc cagaggttcc tgcccaaccc tgctggggtg     1860

cagctggagg accctgagtt ccaggccagc aacatcatgc acagcatcaa tggctatgtg     1920

tttgacagcc tgcagctgtc tgtgtgcctg catgaggtgg cctactggta catcctgagc     1980

attggggccc agactgactt cctgtctgtg ttcttctctg gctacacctt caagcacaag     2040

atggtgtatg aggacaccct gaccctgttc cccttctctg gggagactgt gttcatgagc     2100

atggagaacc ctggcctgtg gattctgggc tgccacaact ctgacttcag gaacaggggc     2160

atgactgccc tgctgaaagt ctccagctgt gacaagaaca ctggggacta ctatgaggac     2220

agctatgagg acatctctgc ctacctgctg agcaagaaca atgccattga gcccaggagc     2280

ttcagccaga atgccactaa tgtgtctaac aacagcaaca ccagcaatga cagcaatgtg     2340

tctcccccag tgctgaagag gcaccagagg gagatcacca ggaccaccct gcagtctgac     2400

caggaggaga ttgactatga tgacaccatc tctgtggaga tgaagaagga ggactttgac     2460

atctacgacg aggacgagaa ccagagcccc aggagcttcc agaagaagac caggcactac     2520

ttcattgctg ctgtggagag gctgtgggac tatggcatga gcagcagccc ccatgtgctg     2580

aggaacaggg cccagtctgg ctctgtgccc cagttcaaga aggtggtgtt ccaggagttc     2640

actgatggca gcttcaccca gcccctgtac agaggggagc tgaatgagca cctgggcctg     2700

ctgggcccct acatcagggc tgaggtggag gacaacatca tggtgacctt caggaaccag     2760

gccagcaggc cctacagctt ctacagcagc ctgatcagct atgaggagga ccagaggcag     2820

ggggctgagc ccaggaagaa ctttgtgaag cccaatgaaa ccaagaccta cttctggaag     2880

gtgcagcacc acatggcccc caccaaggat gagtttgact gcaaggcctg ggcctacttc     2940

tctgatgtgg acctggagaa ggatgtgcac tctggcctga ttggccccct gctggtgtgc     3000

cacaccaaca ccctgaaccc tgcccatggc aggcaggtga ctgtgcagga gtttgccctg     3060

ttcttcacca tctttgatga aaccaagagc tggtacttca ctgagaacat ggagaggaac     3120

tgcagggccc cctgcaacat ccagatggag gaccccacct tcaaggagaa ctacaggttc     3180

catgccatca atggctacat catggacacc ctgcctggcc tggtgatggc ccaggaccag     3240

aggatcaggt ggtacctgct gagcatgggc agcaatgaga acatccacag catccacttc     3300

tctggccatg tgttcactgt gaggaagaag gaggagtaca agatggccct gtacaacctg     3360

taccctgggg tgtttgagac tgtggagatg ctgcccagca aggctggcat ctggagggtg     3420

gagtgcctga ttggggagca cctgcatgct ggcatgagca ccctgttcct ggtgtacagc     3480

aacaagtgcc agacccccct gggcatggcc tctggccaca tcagggactt ccagatcact     3540

gcctctggcc agtatggcca gtgggccccc aagctggcca ggctgcacta ctctggcagc     3600

atcaatgcct ggagcaccaa ggagcccttc agctggatca aggtggacct gctggccccc     3660

atgatcatcc atggcatcaa gacccagggg gccaggcaga agttcagcag cctgtacatc     3720

agccagttca tcatcatgta cagcctggat ggcaagaagt ggcagaccta caggggcaac     3780

agcactggca ccctgatggt gttctttggc aatgtggaca gctctggcat caagcacaac     3840

atcttcaacc cccccatcat tgccagatac atcaggctgc accccaccca ctacagcatc     3900

aggagcaccc tgaggatgga gctgatgggc tgtgacctga acagctgcag catgcccctg     3960

ggcatggaga gcaaggccat ctctgatgcc cagatcactg ccagcagcta cttcaccaac     4020

atgtttgcca cctggagccc cagcaaggcc aggctgcacc tgcagggcag gagcaatgcc     4080

tggaggcccc aggtcaacaa ccccaaggag tggctgcagg tggacttcca gaagaccatg     4140

aaggtgactg gggtgaccac ccagggggtg aagagcctgc tgaccagcat gtatgtgaag     4200

gagttcctga tcagcagcag ccaggatggc caccagtgga ccctgttctt ccagaatggc     4260

aaggtgaagg tgttccaggg caaccaggac agcttcaccc ctgtggtgaa cagcctggac     4320

ccccccctgc tgaccagata cctgaggatt cacccccaga gctgggtgca ccagattgcc     4380

ctgaggatgg aggtgctggg ctgtgaggcc caggacctgt actga                     4425


<210>  4
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Portion of the modified Factor VIII B domain sequence

<400>  4

Ala Thr Asn Val Ser Asn Asn Ser Asn Thr Ser Asn Asp Ser Asn Val 
1               5                   10                  15      


Ser 
    


<210>  5
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII B domain sequence

<400>  5

Ser Phe Ser Gln Asn Ala Thr Asn Val Ser Asn Asn Ser Asn Thr Ser 
1               5                   10                  15      


Asn Asp Ser Asn Val Ser Pro Pro Val Leu Lys Arg His Gln Arg 
            20                  25                  30      


<210>  6
<211>  1474
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Modified Factor VIII sequence

<400>  6

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


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


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


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


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe 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 Ala Thr Asn Val 
        755                 760                 765             


Ser Asn Asn Ser Asn Thr Ser Asn Asp Ser Asn Val Ser Pro Pro Val 
    770                 775                 780                 


Leu Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp 
785                 790                 795                 800 


Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys 
                805                 810                 815     


Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser 
            820                 825                 830         


Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu 
        835                 840                 845             


Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala 
    850                 855                 860                 


Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe 
865                 870                 875                 880 


Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu 
                885                 890                 895     


His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn 
            900                 905                 910         


Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr 
        915                 920                 925             


Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro 
    930                 935                 940                 


Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys 
945                 950                 955                 960 


Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala 
                965                 970                 975     


Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly 
            980                 985                 990         


Leu Ile Gly Pro Leu Leu Val Cys  His Thr Asn Thr Leu  Asn Pro Ala 
        995                 1000                 1005             


His Gly  Arg Gln Val Thr Val  Gln Glu Phe Ala Leu  Phe Phe Thr 
    1010                 1015                 1020             


Ile Phe  Asp Glu Thr Lys Ser  Trp Tyr Phe Thr Glu  Asn Met Glu 
    1025                 1030                 1035             


Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln Met Glu  Asp Pro Thr 
    1040                 1045                 1050             


Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile Asn Gly  Tyr Ile Met 
    1055                 1060                 1065             


Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln Asp Gln  Arg Ile Arg 
    1070                 1075                 1080             


Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu Asn Ile  His Ser Ile 
    1085                 1090                 1095             


His Phe  Ser Gly His Val Phe  Thr Val Arg Lys Lys  Glu Glu Tyr 
    1100                 1105                 1110             


Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly Val Phe  Glu Thr Val 
    1115                 1120                 1125             


Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp Arg Val  Glu Cys Leu 
    1130                 1135                 1140             


Ile Gly  Glu His Leu His Ala  Gly Met Ser Thr Leu  Phe Leu Val 
    1145                 1150                 1155             


Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly Met Ala  Ser Gly His 
    1160                 1165                 1170             


Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly Gln Tyr  Gly Gln Trp 
    1175                 1180                 1185             


Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser Gly Ser  Ile Asn Ala 
    1190                 1195                 1200             


Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile Lys Val  Asp Leu Leu 
    1205                 1210                 1215             


Ala Pro  Met Ile Ile His Gly  Ile Lys Thr Gln Gly  Ala Arg Gln 
    1220                 1225                 1230             


Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe Ile Ile  Met Tyr Ser 
    1235                 1240                 1245             


Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg Gly Asn  Ser Thr Gly 
    1250                 1255                 1260             


Thr Leu  Met Val Phe Phe Gly  Asn Val Asp Ser Ser  Gly Ile Lys 
    1265                 1270                 1275             


His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala Arg Tyr  Ile Arg Leu 
    1280                 1285                 1290             


His Pro  Thr His Tyr Ser Ile  Arg Ser Thr Leu Arg  Met Glu Leu 
    1295                 1300                 1305             


Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met Pro Leu  Gly Met Glu 
    1310                 1315                 1320             


Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr Ala Ser  Ser Tyr Phe 
    1325                 1330                 1335             


Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser Lys Ala  Arg Leu His 
    1340                 1345                 1350             


Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro Gln Val  Asn Asn Pro 
    1355                 1360                 1365             


Lys Glu  Trp Leu Gln Val Asp  Phe Gln Lys Thr Met  Lys Val Thr 
    1370                 1375                 1380             


Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu Leu Thr  Ser Met Tyr 
    1385                 1390                 1395             


Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln Asp Gly  His Gln Trp 
    1400                 1405                 1410             


Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys Val Phe  Gln Gly Asn 
    1415                 1420                 1425             


Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser Leu Asp  Pro Pro Leu 
    1430                 1435                 1440             


Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln Ser Trp  Val His Gln 
    1445                 1450                 1455             


Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys Glu Ala  Gln Asp Leu 
    1460                 1465                 1470             


Tyr 
    


<210>  7
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  B domain linker sequence

<400>  7

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


