                         SEQUENCE LISTING

<110>  Biogen Idec MA Inc.
       DUMONT, Jennifer A.
       LOW, Susan
       BITONTI, Alan J.
       PIERCE, Glenn
       LUK, Alvin
       JIANG, Haiyan
       MCKINNEY, Byron
       OTTMER, Matt
       SOMMER, Jurg
       NUGENT, Karen
       LI, Lian
       PETERS, Robert
 
<120>  Factor VIII Chimeric and Hybrid Polypeptides, and Methods of Use 
       Thereof

<130>  2159.354PC07/EKS/C-K/CMG

<140>  To be assigned
<141>  Herewith

<150>  US 61/657,641
<151>  2012-06-08

<150>  US 61/622,789
<151>  2012-04-11

<150>  US 61/586,443
<151>  2012-01-13

<150>  US 61/569,158 
<151>  2011-12-09

<150>  US 61/541,561
<151>  2011-09-30

<150>  US 61/522,647
<151>  2011-08-11

<150>  US 61/506,015
<151>  2011-07-08

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  5052
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  B-Domain Deleted FVIIIFc Chain


<220>
<221>  misc_feature
<222>  (1)..(57)
<223>  FVIII signal

<220>
<221>  misc_feature
<222>  (4372)..(5052)
<223>  Fc region

<400>  1
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgggcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctgccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctctcaaa acccaccagt cttgaaacgc catcaacggg aaataactcg tactactctt     2340

cagtcagatc aagaggaaat tgactatgat gataccatat cagttgaaat gaagaaggaa     2400

gattttgaca tttatgatga ggatgaaaat cagagccccc gcagctttca aaagaaaaca     2460

cgacactatt ttattgctgc agtggagagg ctctgggatt atgggatgag tagctcccca     2520

catgttctaa gaaacagggc tcagagtggc agtgtccctc agttcaagaa agttgttttc     2580

caggaattta ctgatggctc ctttactcag cccttatacc gtggagaact aaatgaacat     2640

ttgggactcc tggggccata tataagagca gaagttgaag ataatatcat ggtaactttc     2700

agaaatcagg cctctcgtcc ctattccttc tattctagcc ttatttctta tgaggaagat     2760

cagaggcaag gagcagaacc tagaaaaaac tttgtcaagc ctaatgaaac caaaacttac     2820

ttttggaaag tgcaacatca tatggcaccc actaaagatg agtttgactg caaagcctgg     2880

gcttatttct ctgatgttga cctggaaaaa gatgtgcact caggcctgat tggacccctt     2940

ctggtctgcc acactaacac actgaaccct gctcatggga gacaagtgac agtacaggaa     3000

tttgctctgt ttttcaccat ctttgatgag accaaaagct ggtacttcac tgaaaatatg     3060

gaaagaaact gcagggctcc ctgcaatatc cagatggaag atcccacttt taaagagaat     3120

tatcgcttcc atgcaatcaa tggctacata atggatacac tacctggctt agtaatggct     3180

caggatcaaa ggattcgatg gtatctgctc agcatgggca gcaatgaaaa catccattct     3240

attcatttca gtggacatgt gttcactgta cgaaaaaaag aggagtataa aatggcactg     3300

tacaatctct atccaggtgt ttttgagaca gtggaaatgt taccatccaa agctggaatt     3360

tggcgggtgg aatgccttat tggcgagcat ctacatgctg ggatgagcac actttttctg     3420

gtgtacagca ataagtgtca gactcccctg ggaatggctt ctggacacat tagagatttt     3480

cagattacag cttcaggaca atatggacag tgggccccaa agctggccag acttcattat     3540

tccggatcaa tcaatgcctg gagcaccaag gagccctttt cttggatcaa ggtggatctg     3600

ttggcaccaa tgattattca cggcatcaag acccagggtg cccgtcagaa gttctccagc     3660

ctctacatct ctcagtttat catcatgtat agtcttgatg ggaagaagtg gcagacttat     3720

cgaggaaatt ccactggaac cttaatggtc ttctttggca atgtggattc atctgggata     3780

aaacacaata tttttaaccc tccaattatt gctcgataca tccgtttgca cccaactcat     3840

tatagcattc gcagcactct tcgcatggag ttgatgggct gtgatttaaa tagttgcagc     3900

atgccattgg gaatggagag taaagcaata tcagatgcac agattactgc ttcatcctac     3960

tttaccaata tgtttgccac ctggtctcct tcaaaagctc gacttcacct ccaagggagg     4020

agtaatgcct ggagacctca ggtgaataat ccaaaagagt ggctgcaagt ggacttccag     4080

aagacaatga aagtcacagg agtaactact cagggagtaa aatctctgct taccagcatg     4140

tatgtgaagg agttcctcat ctccagcagt caagatggcc atcagtggac tctctttttt     4200

cagaatggca aagtaaaggt ttttcaggga aatcaagact ccttcacacc tgtggtgaac     4260

tctctagacc caccgttact gactcgctac cttcgaattc acccccagag ttgggtgcac     4320

cagattgccc tgaggatgga ggttctgggc tgcgaggcac aggacctcta cgacaaaact     4380

cacacatgcc caccgtgccc agctccagaa ctcctgggcg gaccgtcagt cttcctcttc     4440

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg     4500

gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag     4560

gtgcataatg ccaagacaaa gccgcgggag gagcagtaca acagcacgta ccgtgtggtc     4620

agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc     4680

tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc     4740

cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc     4800

agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc     4860

aatgggcagc cggagaacaa ctacaagacc acgcctcccg tgttggactc cgacggctcc     4920

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc     4980

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg     5040

tctccgggta aa                                                         5052


<210>  2
<211>  1684
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  B domain deleted FVIII-Fc chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(19)
<223>  Signal

<220>
<221>  MISC_FEATURE
<222>  (20)..(753)
<223>  Heavy chain (HC)

<220>
<221>  MISC_FEATURE
<222>  (760)..(773)
<223>  B domain

<220>
<221>  MISC_FEATURE
<222>  (1457)..(1684)
<223>  Fc region

<400>  2

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


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


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


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


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


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


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


Asp Leu Ala Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu 
                565                 570                 575     


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
        755                 760                 765             


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 


Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu 
785                 790                 795                 800 


Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe 
                805                 810                 815     


Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
            820                 825                 830         


Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln 
        835                 840                 845             


Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
    850                 855                 860                 


Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His 
865                 870                 875                 880 


Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile 
                885                 890                 895     


Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
            900                 905                 910         


Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg 
        915                 920                 925             


Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val 
    930                 935                 940                 


Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp 
945                 950                 955                 960 


Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
                965                 970                 975     


Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His 
            980                 985                 990         


Gly Arg Gln Val Thr Val Gln Glu  Phe Ala Leu Phe Phe  Thr Ile Phe 
        995                 1000                 1005             


Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu Asn Met  Glu Arg Asn 
    1010                 1015                 1020             


Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu Asp Pro  Thr Phe Lys 
    1025                 1030                 1035             


Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly Tyr Ile  Met Asp Thr 
    1040                 1045                 1050             


Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln Arg Ile  Arg Trp Tyr 
    1055                 1060                 1065             


Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile His Ser  Ile His Phe 
    1070                 1075                 1080             


Ser Gly  His Val Phe Thr Val  Arg Lys Lys Glu Glu  Tyr Lys Met 
    1085                 1090                 1095             


Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe Glu Thr  Val Glu Met 
    1100                 1105                 1110             


Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val Glu Cys  Leu Ile Gly 
    1115                 1120                 1125             


Glu His  Leu His Ala Gly Met  Ser Thr Leu Phe Leu  Val Tyr Ser 
    1130                 1135                 1140             


Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala Ser Gly  His Ile Arg 
    1145                 1150                 1155             


Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr Gly Gln  Trp Ala Pro 
    1160                 1165                 1170             


Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser Ile Asn  Ala Trp Ser 
    1175                 1180                 1185             


Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val Asp Leu  Leu Ala Pro 
    1190                 1195                 1200             


Met Ile  Ile His Gly Ile Lys  Thr Gln Gly Ala Arg  Gln Lys Phe 
    1205                 1210                 1215             


Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile Met Tyr  Ser Leu Asp 
    1220                 1225                 1230             


Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn Ser Thr  Gly Thr Leu 
    1235                 1240                 1245             


Met Val  Phe Phe Gly Asn Val  Asp Ser Ser Gly Ile  Lys His Asn 
    1250                 1255                 1260             


Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr Ile Arg  Leu His Pro 
    1265                 1270                 1275             


Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg Met Glu  Leu Met Gly 
    1280                 1285                 1290             


Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu Gly Met  Glu Ser Lys 
    1295                 1300                 1305             


Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser Ser Tyr  Phe Thr Asn 
    1310                 1315                 1320             


Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala Arg Leu  His Leu Gln 
    1325                 1330                 1335             


Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val Asn Asn  Pro Lys Glu 
    1340                 1345                 1350             


Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met Lys Val  Thr Gly Val 
    1355                 1360                 1365             


Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr Ser Met  Tyr Val Lys 
    1370                 1375                 1380             


Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly His Gln  Trp Thr Leu 
    1385                 1390                 1395             


Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe Gln Gly  Asn Gln Asp 
    1400                 1405                 1410             


Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp Pro Pro  Leu Leu Thr 
    1415                 1420                 1425             


Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp Val His  Gln Ile Ala 
    1430                 1435                 1440             


Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala Gln Asp  Leu Tyr Asp 
    1445                 1450                 1455             


Lys Thr  His Thr Cys Pro Pro  Cys Pro Ala Pro Glu  Leu Leu Gly 
    1460                 1465                 1470             


Gly Pro  Ser Val Phe Leu Phe  Pro Pro Lys Pro Lys  Asp Thr Leu 
    1475                 1480                 1485             


Met Ile  Ser Arg Thr Pro Glu  Val Thr Cys Val Val  Val Asp Val 
    1490                 1495                 1500             


Ser His  Glu Asp Pro Glu Val  Lys Phe Asn Trp Tyr  Val Asp Gly 
    1505                 1510                 1515             


Val Glu  Val His Asn Ala Lys  Thr Lys Pro Arg Glu  Glu Gln Tyr 
    1520                 1525                 1530             


Asn Ser  Thr Tyr Arg Val Val  Ser Val Leu Thr Val  Leu His Gln 
    1535                 1540                 1545             


Asp Trp  Leu Asn Gly Lys Glu  Tyr Lys Cys Lys Val  Ser Asn Lys 
    1550                 1555                 1560             


Ala Leu  Pro Ala Pro Ile Glu  Lys Thr Ile Ser Lys  Ala Lys Gly 
    1565                 1570                 1575             


Gln Pro  Arg Glu Pro Gln Val  Tyr Thr Leu Pro Pro  Ser Arg Asp 
    1580                 1585                 1590             


Glu Leu  Thr Lys Asn Gln Val  Ser Leu Thr Cys Leu  Val Lys Gly 
    1595                 1600                 1605             


Phe Tyr  Pro Ser Asp Ile Ala  Val Glu Trp Glu Ser  Asn Gly Gln 
    1610                 1615                 1620             


Pro Glu  Asn Asn Tyr Lys Thr  Thr Pro Pro Val Leu  Asp Ser Asp 
    1625                 1630                 1635             


Gly Ser  Phe Phe Leu Tyr Ser  Lys Leu Thr Val Asp  Lys Ser Arg 
    1640                 1645                 1650             


Trp Gln  Gln Gly Asn Val Phe  Ser Cys Ser Val Met  His Glu Ala 
    1655                 1660                 1665             


Leu His  Asn His Tyr Thr Gln  Lys Ser Leu Ser Leu  Ser Pro Gly 
    1670                 1675                 1680             


Lys 
    


<210>  3
<211>  741
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fc region


<220>
<221>  misc_signal
<222>  (1)..(60)
<223>  Mouse Ig kappa signal

<400>  3
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt       60

gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggagg accgtcagtc      120

ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca      180

tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac      240

ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac      300

cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag      360

tgcaaggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa      420

gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgcgatga gctgaccaag      480

aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag      540

tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gttggactcc      600

gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg      660

aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc      720

ctctccctgt ctccgggtaa a                                                741


<210>  4
<211>  247
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(20)
<223>  heterologous signal from Mouse Ig kappa chain

<400>  4

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
            20                  25                  30          


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        35                  40                  45              


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    50                  55                  60                  


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
65                  70                  75                  80  


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
                85                  90                  95      


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            100                 105                 110         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
        115                 120                 125             


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    130                 135                 140                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
145                 150                 155                 160 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                165                 170                 175     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            180                 185                 190         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        195                 200                 205             


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
    210                 215                 220                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
225                 230                 235                 240 


Leu Ser Leu Ser Pro Gly Lys 
                245         


<210>  5
<211>  7734
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Full length FVIIIFc


<220>
<221>  misc_signal
<222>  (1)..(57)
<223>  FVIII signal

<220>
<221>  misc_feature
<222>  (7054)..(7734)
<223>  Fc region

<400>  5
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgggcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctgccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctcccaga attcaagaca ccctagcact aggcaaaagc aatttaatgc caccacaatt     2340

ccagaaaatg acatagagaa gactgaccct tggtttgcac acagaacacc tatgcctaaa     2400

atacaaaatg tctcctctag tgatttgttg atgctcttgc gacagagtcc tactccacat     2460

gggctatcct tatctgatct ccaagaagcc aaatatgaga ctttttctga tgatccatca     2520

cctggagcaa tagacagtaa taacagcctg tctgaaatga cacacttcag gccacagctc     2580

catcacagtg gggacatggt atttacccct gagtcaggcc tccaattaag attaaatgag     2640

aaactgggga caactgcagc aacagagttg aagaaacttg atttcaaagt ttctagtaca     2700

tcaaataatc tgatttcaac aattccatca gacaatttgg cagcaggtac tgataataca     2760

agttccttag gacccccaag tatgccagtt cattatgata gtcaattaga taccactcta     2820

tttggcaaaa agtcatctcc ccttactgag tctggtggac ctctgagctt gagtgaagaa     2880

aataatgatt caaagttgtt agaatcaggt ttaatgaata gccaagaaag ttcatgggga     2940

aaaaatgtat cgtcaacaga gagtggtagg ttatttaaag ggaaaagagc tcatggacct     3000

gctttgttga ctaaagataa tgccttattc aaagttagca tctctttgtt aaagacaaac     3060

aaaacttcca ataattcagc aactaataga aagactcaca ttgatggccc atcattatta     3120

attgagaata gtccatcagt ctggcaaaat atattagaaa gtgacactga gtttaaaaaa     3180

gtgacacctt tgattcatga cagaatgctt atggacaaaa atgctacagc tttgaggcta     3240

aatcatatgt caaataaaac tacttcatca aaaaacatgg aaatggtcca acagaaaaaa     3300

gagggcccca ttccaccaga tgcacaaaat ccagatatgt cgttctttaa gatgctattc     3360

ttgccagaat cagcaaggtg gatacaaagg actcatggaa agaactctct gaactctggg     3420

caaggcccca gtccaaagca attagtatcc ttaggaccag aaaaatctgt ggaaggtcag     3480

aatttcttgt ctgagaaaaa caaagtggta gtaggaaagg gtgaatttac aaaggacgta     3540

ggactcaaag agatggtttt tccaagcagc agaaacctat ttcttactaa cttggataat     3600

ttacatgaaa ataatacaca caatcaagaa aaaaaaattc aggaagaaat agaaaagaag     3660

gaaacattaa tccaagagaa tgtagttttg cctcagatac atacagtgac tggcactaag     3720

aatttcatga agaacctttt cttactgagc actaggcaaa atgtagaagg ttcatatgac     3780

ggggcatatg ctccagtact tcaagatttt aggtcattaa atgattcaac aaatagaaca     3840

aagaaacaca cagctcattt ctcaaaaaaa ggggaggaag aaaacttgga aggcttggga     3900

aatcaaacca agcaaattgt agagaaatat gcatgcacca caaggatatc tcctaataca     3960

agccagcaga attttgtcac gcaacgtagt aagagagctt tgaaacaatt cagactccca     4020

ctagaagaaa cagaacttga aaaaaggata attgtggatg acacctcaac ccagtggtcc     4080

aaaaacatga aacatttgac cccgagcacc ctcacacaga tagactacaa tgagaaggag     4140

aaaggggcca ttactcagtc tcccttatca gattgcctta cgaggagtca tagcatccct     4200

caagcaaata gatctccatt acccattgca aaggtatcat catttccatc tattagacct     4260

atatatctga ccagggtcct attccaagac aactcttctc atcttccagc agcatcttat     4320

agaaagaaag attctggggt ccaagaaagc agtcatttct tacaaggagc caaaaaaaat     4380

aacctttctt tagccattct aaccttggag atgactggtg atcaaagaga ggttggctcc     4440

ctggggacaa gtgccacaaa ttcagtcaca tacaagaaag ttgagaacac tgttctcccg     4500

aaaccagact tgcccaaaac atctggcaaa gttgaattgc ttccaaaagt tcacatttat     4560

cagaaggacc tattccctac ggaaactagc aatgggtctc ctggccatct ggatctcgtg     4620

gaagggagcc ttcttcaggg aacagaggga gcgattaagt ggaatgaagc aaacagacct     4680

ggaaaagttc cctttctgag agtagcaaca gaaagctctg caaagactcc ctccaagcta     4740

ttggatcctc ttgcttggga taaccactat ggtactcaga taccaaaaga agagtggaaa     4800

tcccaagaga agtcaccaga aaaaacagct tttaagaaaa aggataccat tttgtccctg     4860

aacgcttgtg aaagcaatca tgcaatagca gcaataaatg agggacaaaa taagcccgaa     4920

atagaagtca cctgggcaaa gcaaggtagg actgaaaggc tgtgctctca aaacccacca     4980

gtcttgaaac gccatcaacg ggaaataact cgtactactc ttcagtcaga tcaagaggaa     5040

attgactatg atgataccat atcagttgaa atgaagaagg aagattttga catttatgat     5100

gaggatgaaa atcagagccc ccgcagcttt caaaagaaaa cacgacacta ttttattgct     5160

gcagtggaga ggctctggga ttatgggatg agtagctccc cacatgttct aagaaacagg     5220

gctcagagtg gcagtgtccc tcagttcaag aaagttgttt tccaggaatt tactgatggc     5280

tcctttactc agcccttata ccgtggagaa ctaaatgaac atttgggact cctggggcca     5340

tatataagag cagaagttga agataatatc atggtaactt tcagaaatca ggcctctcgt     5400

ccctattcct tctattctag ccttatttct tatgaggaag atcagaggca aggagcagaa     5460

cctagaaaaa actttgtcaa gcctaatgaa accaaaactt acttttggaa agtgcaacat     5520

catatggcac ccactaaaga tgagtttgac tgcaaagcct gggcttattt ctctgatgtt     5580

gacctggaaa aagatgtgca ctcaggcctg attggacccc ttctggtctg ccacactaac     5640

acactgaacc ctgctcatgg gagacaagtg acagtacagg aatttgctct gtttttcacc     5700

atctttgatg agaccaaaag ctggtacttc actgaaaata tggaaagaaa ctgcagggct     5760

ccctgcaata tccagatgga agatcccact tttaaagaga attatcgctt ccatgcaatc     5820

aatggctaca taatggatac actacctggc ttagtaatgg ctcaggatca aaggattcga     5880

tggtatctgc tcagcatggg cagcaatgaa aacatccatt ctattcattt cagtggacat     5940

gtgttcactg tacgaaaaaa agaggagtat aaaatggcac tgtacaatct ctatccaggt     6000

gtttttgaga cagtggaaat gttaccatcc aaagctggaa tttggcgggt ggaatgcctt     6060

attggcgagc atctacatgc tgggatgagc acactttttc tggtgtacag caataagtgt     6120

cagactcccc tgggaatggc ttctggacac attagagatt ttcagattac agcttcagga     6180

caatatggac agtgggcccc aaagctggcc agacttcatt attccggatc aatcaatgcc     6240

tggagcacca aggagccctt ttcttggatc aaggtggatc tgttggcacc aatgattatt     6300

cacggcatca agacccaggg tgcccgtcag aagttctcca gcctctacat ctctcagttt     6360

atcatcatgt atagtcttga tgggaagaag tggcagactt atcgaggaaa ttccactgga     6420

accttaatgg tcttctttgg caatgtggat tcatctggga taaaacacaa tatttttaac     6480

cctccaatta ttgctcgata catccgtttg cacccaactc attatagcat tcgcagcact     6540

cttcgcatgg agttgatggg ctgtgattta aatagttgca gcatgccatt gggaatggag     6600

agtaaagcaa tatcagatgc acagattact gcttcatcct actttaccaa tatgtttgcc     6660

acctggtctc cttcaaaagc tcgacttcac ctccaaggga ggagtaatgc ctggagacct     6720

caggtgaata atccaaaaga gtggctgcaa gtggacttcc agaagacaat gaaagtcaca     6780

ggagtaacta ctcagggagt aaaatctctg cttaccagca tgtatgtgaa ggagttcctc     6840

atctccagca gtcaagatgg ccatcagtgg actctctttt ttcagaatgg caaagtaaag     6900

gtttttcagg gaaatcaaga ctccttcaca cctgtggtga actctctaga cccaccgtta     6960

ctgactcgct accttcgaat tcacccccag agttgggtgc accagattgc cctgaggatg     7020

gaggttctgg gctgcgaggc acaggacctc tacgacaaaa ctcacacatg cccaccgtgc     7080

ccagctccag aactcctggg cggaccgtca gtcttcctct tccccccaaa acccaaggac     7140

accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa     7200

gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca     7260

aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg     7320

caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca     7380

gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac     7440

accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc     7500

aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac     7560

aactacaaga ccacgcctcc cgtgttggac tccgacggct ccttcttcct ctacagcaag     7620

ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat     7680

gaggctctgc acaaccacta cacgcagaag agcctctccc tgtctccggg taaa           7734


<210>  6
<211>  2578
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Full length FVIIIFc chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(19)
<223>  FVIII signal

<220>
<221>  MISC_FEATURE
<222>  (20)..(759)
<223>  HC

<220>
<221>  MISC_FEATURE
<222>  (760)..(1667)
<223>  B domain

<220>
<221>  MISC_FEATURE
<222>  (2352)..(2578)
<223>  Fc region

<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 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 Asp Lys Thr His  Thr Cys Pro 
    2345                 2350                 2355             


Pro Cys  Pro Ala Pro Glu Leu  Leu Gly Gly Pro Ser  Val Phe Leu 
    2360                 2365                 2370             


Phe Pro  Pro Lys Pro Lys Asp  Thr Leu Met Ile Ser  Arg Thr Pro 
    2375                 2380                 2385             


Glu Val  Thr Cys Val Val Val  Asp Val Ser His Glu  Asp Pro Glu 
    2390                 2395                 2400             


Val Lys  Phe Asn Trp Tyr Val  Asp Gly Val Glu Val  His Asn Ala 
    2405                 2410                 2415             


Lys Thr  Lys Pro Arg Glu Glu  Gln Tyr Asn Ser Thr  Tyr Arg Val 
    2420                 2425                 2430             


Val Ser  Val Leu Thr Val Leu  His Gln Asp Trp Leu  Asn Gly Lys 
    2435                 2440                 2445             


Glu Tyr  Lys Cys Lys Val Ser  Asn Lys Ala Leu Pro  Ala Pro Ile 
    2450                 2455                 2460             


Glu Lys  Thr Ile Ser Lys Ala  Lys Gly Gln Pro Arg  Glu Pro Gln 
    2465                 2470                 2475             


Val Tyr  Thr Leu Pro Pro Ser  Arg Asp Glu Leu Thr  Lys Asn Gln 
    2480                 2485                 2490             


Val Ser  Leu Thr Cys Leu Val  Lys Gly Phe Tyr Pro  Ser Asp Ile 
    2495                 2500                 2505             


Ala Val  Glu Trp Glu Ser Asn  Gly Gln Pro Glu Asn  Asn Tyr Lys 
    2510                 2515                 2520             


Thr Thr  Pro Pro Val Leu Asp  Ser Asp Gly Ser Phe  Phe Leu Tyr 
    2525                 2530                 2535             


Ser Lys  Leu Thr Val Asp Lys  Ser Arg Trp Gln Gln  Gly Asn Val 
    2540                 2545                 2550             


Phe Ser  Cys Ser Val Met His  Glu Ala Leu His Asn  His Tyr Thr 
    2555                 2560                 2565             


Gln Lys  Ser Leu Ser Leu Ser  Pro Gly Lys 
    2570                 2575             


<210>  7
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  albumin-binding peptide

<400>  7

Asp Ile Cys Leu Pro Arg Trp Gly Cys Leu Trp 
1               5                   10      


<210>  8
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP peptide

<400>  8

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


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


<210>  9
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP Petptide

<400>  9

Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg 
1               5                   10                  15      


Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln 
            20                  25              


<210>  10
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  10

Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro 
1               5                   10                  15      


Ser Ala Pro Ala 
            20  


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

<220>
<223>  PAS peptide

<400>  11

Ala Ala Pro Ala Ser Pro Ala Pro Ala Ala Pro Ser Ala Pro Ala Pro 
1               5                   10                  15      


Ala Ala Pro Ser 
            20  


<210>  12
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  12

Ala Pro Ser Ser Pro Ser Pro Ser Ala Pro Ser Ser Pro Ser Pro Ala 
1               5                   10                  15      


Ser Pro Ser Ser 
            20  


<210>  13
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  13

Ala Pro Ser Ser Pro Ser Pro Ser Ala Pro Ser Ser Pro Ser Pro Ala 
1               5                   10                  15      


Ser Pro Ser 
            


<210>  14
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  14

Ser Ser Pro Ser Ala Pro Ser Pro Ser Ser Pro Ala Ser Pro Ser Pro 
1               5                   10                  15      


Ser Ser Pro Ala 
            20  


<210>  15
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  15

Ala Ala Ser Pro Ala Ala Pro Ser Ala Pro Pro Ala Ala Ala Ser Pro 
1               5                   10                  15      


Ala Ala Pro Ser Ala Pro Pro Ala 
            20                  


<210>  16
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  16

Ala Ser Ala Ala Ala Pro Ala Ala Ala Ser Ala Ala Ala Ser Ala Pro 
1               5                   10                  15      


Ser Ala Ala Ala 
            20  


