                         SEQUENCE LISTING

<110>  JIANG, HAIYAN
 
<120>  POPULATION PHARMACOKINETICS TOOLS AND USES THEREOF

<130>  2159.4300002/C-K/BMB

<140>  To be assigned
<141>  2014-02-25

<160>  21    

<170>  PatentIn version 3.5

<210>  1
<211>  7583
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pSYN-FIX-030

<400>  1
gcgcgcgttg acattgatta ttgactagtt attaatagta atcaattacg gggtcattag       60

ttcatagccc atatatggag ttccgcgtta cataacttac ggtaaatggc ccgcctggct      120

gaccgcccaa cgacccccgc ccattgacgt caataatgac gtatgttccc atagtaacgc      180

caatagggac tttccattga cgtcaatggg tggagtattt acggtaaact gcccacttgg      240

cagtacatca agtgtatcat atgccaagta cgccccctat tgacgtcaat gacggtaaat      300

ggcccgcctg gcattatgcc cagtacatga ccttatggga ctttcctact tggcagtaca      360

tctacgtatt agtcatcgct attaccatgg tgatgcggtt ttggcagtac atcaatgggc      420

gtggatagcg gtttgactca cggggatttc caagtctcca ccccattgac gtcaatggga      480

gtttgttttg gcaccaaaat caacgggact ttccaaaatg tcgtaacaac tccgccccat      540

tgacgcaaat gggcggtagg cgtgtacggt gggaggtcta tataagcaga gctctctggc      600

taactagaga acccactgct tactggctta tcgaaattaa tacgactcac tatagggaga      660

cccaagcttc gcgacgtacg gccgccacca tgcagcgcgt gaacatgatc atggcagaat      720

caccaggcct catcaccatc tgccttttag gatatctact cagtgctgaa tgtacaggtt      780

tgtttccttt tttaaaatac attgagtatg cttgcctttt agatatagaa atatctgatg      840

ctgtcttctt cactaaattt tgattacatg atttgacagc aatattgaag agtctaacag      900

ccagcacgca ggttggtaag tactgtggga acatcacaga ttttggctcc atgccctaaa      960

gagaaattgg ctttcagatt atttggatta aaaacaaaga ctttcttaag agatgtaaaa     1020

ttttcatgat gttttctttt ttgctaaaac taaagaatta ttcttttaca tttcagtttt     1080

tcttgatcat gaaaacgcca acaaaattct gaatcggcca aagaggtata attcaggtaa     1140

attggaagag tttgttcaag ggaatctaga gagagaatgt atggaagaaa agtgtagttt     1200

tgaagaagca cgagaagttt ttgaaaacac tgaaagaaca actgaatttt ggaagcagta     1260

tgttgatgga gatcagtgtg agtccaatcc atgtttaaat ggcggcagtt gcaaggatga     1320

cattaattcc tatgaatgtt ggtgtccctt tggatttgaa ggaaagaact gtgaattaga     1380

tgtaacatgt aacattaaga atggcagatg cgagcagttt tgtaaaaata gtgctgataa     1440

caaggtggtt tgctcctgta ctgagggata tcgacttgca gaaaaccaga agtcctgtga     1500

accagcagtg ccatttccat gtggaagagt ttctgtttca caaacttcta agctcacccg     1560

tgctgagact gtttttcctg atgtggacta tgtaaattct actgaagctg aaaccatttt     1620

ggataacatc actcaaagca cccaatcatt taatgacttc actcgggttg ttggtggaga     1680

agatgccaaa ccaggtcaat tcccttggca ggttgttttg aatggtaaag ttgatgcatt     1740

ctgtggaggc tctatcgtta atgaaaaatg gattgtaact gctgcccact gtgttgaaac     1800

tggtgttaaa attacagttg tcgcaggtga acataatatt gaggagacag aacatacaga     1860

gcaaaagcga aatgtgattc gaattattcc tcaccacaac tacaatgcag ctattaataa     1920

gtacaaccat gacattgccc ttctggaact ggacgaaccc ttagtgctaa acagctacgt     1980

tacacctatt tgcattgctg acaaggaata cacgaacatc ttcctcaaat ttggatctgg     2040

ctatgtaagt ggctggggaa gagtcttcca caaagggaga tcagctttag ttcttcagta     2100

ccttagagtt ccacttgttg accgagccac atgtcttcga tctacaaagt tcaccatcta     2160

taacaacatg ttctgtgctg gcttccatga aggaggtaga gattcatgtc aaggagatag     2220

tgggggaccc catgttactg aagtggaagg gaccagtttc ttaactggaa ttattagctg     2280

gggtgaagag tgtgcaatga aaggcaaata tggaatatat accaaggtgt cccggtatgt     2340

caactggatt aaggaaaaaa caaagctcac tgacaaaact cacacatgcc caccgtgccc     2400

agctccggaa ctcctgggcg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac     2460

cctcatgatc tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga     2520

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa     2580

gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca     2640

ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc     2700

ccccatcgag aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac     2760

cctgccccca tcccgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa     2820

aggcttctat cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa     2880

ctacaagacc acgcctcccg tgttggactc cgacggctcc ttcttcctct acagcaagct     2940

caccgtggac aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga     3000

ggctctgcac aaccactaca cgcagaagag cctctccctg tctccgggta aatgagaatt     3060

cagacatgat aagatacatt gatgagtttg gacaaaccac aactagaatg cagtgaaaaa     3120

aatgctttat ttgtgaaatt tgtgatgcta ttgctttatt tgtaaccatt ataagctgca     3180

ataaacaagt tggggtgggc gaagaactcc agcatgagat ccccgcgctg gaggatcatc     3240

cagccggcgt cccggaaaac gattccgaag cccaaccttt catagaaggc ggcggtggaa     3300

tcgaaatctc gtagcacgtg tcagtcctgc tcctcggcca cgaagtgcac gcagttgccg     3360

gccgggtcgc gcagggcgaa ctcccgcccc cacggctgct cgccgatctc ggtcatggcc     3420

ggcccggagg cgtcccggaa gttcgtggac acgacctccg accactcggc gtacagctcg     3480

tccaggccgc gcacccacac ccaggccagg gtgttgtccg gcaccacctg gtcctggacc     3540

gcgctgatga acagggtcac gtcgtcccgg accacaccgg cgaagtcgtc ctccacgaag     3600

tcccgggaga acccgagccg gtcggtccag aactcgaccg ctccggcgac gtcgcgcgcg     3660

gtgagcaccg gaacggcact ggtcaacttg gccatggttt agttcctcac cttgtcgtat     3720

tatactatgc cgatatacta tgccgatgat taattgtcaa cacgtgctga tcagatccga     3780

aaatggatat acaagctccc gggagctttt tgcaaaagcc taggcctcca aaaaagcctc     3840

ctcactactt ctggaatagc tcagaggcag aggcggcctc ggcctctgca taaataaaaa     3900

aaattagtca gccatggggc ggagaatggg cggaactggg cggagttagg ggcgggatgg     3960

gcggagttag gggcgggact atggttgctg actaattgag atgcatgctt tgcatacttc     4020

tgcctgctgg ggagcctggg gactttccac acctggttgc tgactaattg agatgcatgc     4080

tttgcatact tctgcctgct ggggagcctg gggactttcc acaccctcgt cgagctagct     4140

tcgtgaggct ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag     4200

ttggggggag gggtcggcaa ttgaaccggt gcctagagaa ggtggcgcgg ggtaaactgg     4260

gaaagtgatg tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata     4320

agtgcagtag tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggta     4380

agtgccgtgt gtggttcccg cgggcctggc ctctttacgg gttatggccc ttgcgtgcct     4440

tgaattactt ccacctggct ccagtacgtg attcttgatc ccgagctgga gccaggggcg     4500

ggccttgcgc tttaggagcc ccttcgcctc gtgcttgagt tgaggcctgg cctgggcgct     4560

ggggccgccg cgtgcgaatc tggtggcacc ttcgcgcctg tctcgctgct ttcgataagt     4620

ctctagccat ttaaaatttt tgatgacctg ctgcgacgct ttttttctgg caagatagtc     4680

ttgtaaatgc gggccaggat ctgcacactg gtatttcggt ttttggggcc gcgggcggcg     4740

acggggcccg tgcgtcccag cgcacatgtt cggcgaggcg gggcctgcga gcgcggccac     4800

cgagaatcgg acgggggtag tctcaagctg gccggcctgc tctggtgcct ggcctcgcgc     4860

cgccgtgtat cgccccgccc tgggcggcaa ggctggcccg gtcggcacca gttgcgtgag     4920

cggaaagatg gccgcttccc ggccctgctc cagggggctc aaaatggagg acgcggcgct     4980

cgggagagcg ggcgggtgag tcacccacac aaaggaaagg ggcctttccg tcctcagccg     5040

tcgcttcatg tgactccacg gagtaccggg cgccgtccag gcacctcgat tagttctgga     5100

gcttttggag tacgtcgtct ttaggttggg gggaggggtt ttatgcgatg gagtttcccc     5160

acactgagtg ggtggagact gaagttaggc cagcttggca cttgatgtaa ttctccttgg     5220

aatttgccct ttttgagttt ggatcttggt tcattctcaa gcctcagaca gtggttcaaa     5280

gtttttttct tccatttcag gtgtcgtgaa cacgtggtcg cggccgcgcc gccaccatgg     5340

agacagacac actcctgcta tgggtactgc tgctctgggt tccaggttcc actggtgaca     5400

aaactcacac atgcccaccg tgcccagcac ctgaactcct gggaggaccg tcagtcttcc     5460

tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag gtcacatgcg     5520

tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac gtggacggcg     5580

tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc acgtaccgtg     5640

tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag tacaagtgca     5700

aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa gccaaagggc     5760

agccccgaga accacaggtg tacaccctgc ccccatcccg cgatgagctg accaagaacc     5820

aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc gtggagtggg     5880

agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgttg gactccgacg     5940

gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag caggggaacg     6000

tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag aagagcctct     6060

ccctgtctcc gggtaaatga ctcgagagat ctggccggct gggcccgttt cgaaggtaag     6120

cctatcccta accctctcct cggtctcgat tctacgcgta ccggtcatca tcaccatcac     6180

cattgagttt aaacccgctg atcagcctcg actgtgcctt ctagttgcca gccatctgtt     6240

gtttgcccct cccccgtgcc ttccttgacc ctggaaggtg ccactcccac tgtcctttcc     6300

taataaaatg aggaaattgc atcgcattgt ctgagtaggt gtcattctat tctggggggt     6360

ggggtggggc aggacagcaa gggggaggat tgggaagaca atagcaggca tgctggggat     6420

gcggtgggct ctatggcttc tgaggcggaa agaaccagtg gcggtaatac ggttatccac     6480

agaatcaggg gataacgcag gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa     6540

ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc cgcccccctg acgagcatca     6600

caaaaatcga cgctcaagtc agaggtggcg aaacccgaca ggactataaa gataccaggc     6660

gtttccccct agaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata     6720

cctgtccgcc tttctccctt cgggaagcgt ggcgctttct catagctcac gctgtaggta     6780

tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca     6840

gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga     6900

cttatcgcca ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg     6960

tgctacagag ttcttgaagt ggtggcctaa ctacggctac actagaagaa cagtatttgg     7020

tatctgcgct ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg     7080

caaacaaacc accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag     7140

aaaaaaagga tctcaagaag atcctttgat cttttctacg gggtctgacg ctcagtggaa     7200

cgaaaactca cgttaaggga ttttggtcat gacattaacc tataaaaata ggcgtatcac     7260

gaggcccttt cgtctcgcgc gtttcggtga tgacggtgaa aacctctgac acatgcagct     7320

cccggagacg gtcacagctt gtctgtaagc ggatgccggg agcagacaag cccgtcaggg     7380

cgcgtcagcg ggtgttggcg ggtgtcgggg ctggcttaac tatgcggcat cagagcagat     7440

tgtactgaga gtgcaccata tatgcggtgt gaaataccgc acagatgcgt aaggagaaaa     7500

taccgcatca ggcgccattc gccattcagg ctgcgcaact gttgggaagg gcgatcggtg     7560

cgggcctctt cgctattacg cca                                             7583


<210>  2
<211>  688
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  pSYN-FIX-030


<220>
<221>  SIGNAL
<222>  (-46)..(-19)

220>
<221>  SIGNAL
<222>  (-18)..(-1)

<220>
<221>  mat_peptide
<222>  (1)..(642)

<400>  2

Met Gln Arg Val Asn Met Ile Met Ala Glu Ser Pro Gly Leu Ile Thr 
    -45                 -40                 -35                 


Ile Cys Leu Leu Gly Tyr Leu Leu Ser Ala Glu Cys Thr Val Phe Leu 
-30                 -25                 -20                 -15 


Asp His Glu Asn Ala Asn Lys Ile Leu Asn Arg Pro Lys Arg Tyr Asn 
                -10                 -5              -1  1       


Ser Gly Lys Leu Glu Glu Phe Val Gln Gly Asn Leu Glu Arg Glu Cys 
        5                   10                  15              


Met Glu Glu Lys Cys Ser Phe Glu Glu Ala Arg Glu Val Phe Glu Asn 
    20                  25                  30                  


Thr Glu Arg Thr Thr Glu Phe Trp Lys Gln Tyr Val Asp Gly Asp Gln 
35                  40                  45                  50  


Cys Glu Ser Asn Pro Cys Leu Asn Gly Gly Ser Cys Lys Asp Asp Ile 
                55                  60                  65      


Asn Ser Tyr Glu Cys Trp Cys Pro Phe Gly Phe Glu Gly Lys Asn Cys 
            70                  75                  80          


Glu Leu Asp Val Thr Cys Asn Ile Lys Asn Gly Arg Cys Glu Gln Phe 
        85                  90                  95              


Cys Lys Asn Ser Ala Asp Asn Lys Val Val Cys Ser Cys Thr Glu Gly 
    100                 105                 110                 


Tyr Arg Leu Ala Glu Asn Gln Lys Ser Cys Glu Pro Ala Val Pro Phe 
115                 120                 125                 130 


Pro Cys Gly Arg Val Ser Val Ser Gln Thr Ser Lys Leu Thr Arg Ala 
                135                 140                 145     


Glu Thr Val Phe Pro Asp Val Asp Tyr Val Asn Ser Thr Glu Ala Glu 
            150                 155                 160         


Thr Ile Leu Asp Asn Ile Thr Gln Ser Thr Gln Ser Phe Asn Asp Phe 
        165                 170                 175             


Thr Arg Val Val Gly Gly Glu Asp Ala Lys Pro Gly Gln Phe Pro Trp 
    180                 185                 190                 


Gln Val Val Leu Asn Gly Lys Val Asp Ala Phe Cys Gly Gly Ser Ile 
195                 200                 205                 210 


Val Asn Glu Lys Trp Ile Val Thr Ala Ala His Cys Val Glu Thr Gly 
                215                 220                 225     


Val Lys Ile Thr Val Val Ala Gly Glu His Asn Ile Glu Glu Thr Glu 
            230                 235                 240         


His Thr Glu Gln Lys Arg Asn Val Ile Arg Ile Ile Pro His His Asn 
        245                 250                 255             


Tyr Asn Ala Ala Ile Asn Lys Tyr Asn His Asp Ile Ala Leu Leu Glu 
    260                 265                 270                 


Leu Asp Glu Pro Leu Val Leu Asn Ser Tyr Val Thr Pro Ile Cys Ile 
275                 280                 285                 290 


Ala Asp Lys Glu Tyr Thr Asn Ile Phe Leu Lys Phe Gly Ser Gly Tyr 
                295                 300                 305     


Val Ser Gly Trp Gly Arg Val Phe His Lys Gly Arg Ser Ala Leu Val 
            310                 315                 320         


Leu Gln Tyr Leu Arg Val Pro Leu Val Asp Arg Ala Thr Cys Leu Arg 
        325                 330                 335             


Ser Thr Lys Phe Thr Ile Tyr Asn Asn Met Phe Cys Ala Gly Phe His 
    340                 345                 350                 


Glu Gly Gly Arg Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro His Val 
355                 360                 365                 370 


Thr Glu Val Glu Gly Thr Ser Phe Leu Thr Gly Ile Ile Ser Trp Gly 
                375                 380                 385     


Glu Glu Cys Ala Met Lys Gly Lys Tyr Gly Ile Tyr Thr Lys Val Ser 
            390                 395                 400         


Arg Tyr Val Asn Trp Ile Lys Glu Lys Thr Lys Leu Thr Asp Lys Thr 
        405                 410                 415             


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
    420                 425                 430                 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
435                 440                 445                 450 


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                455                 460                 465     


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
            470                 475                 480         


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
        485                 490                 495             


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
    500                 505                 510                 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
515                 520                 525                 530 


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
                535                 540                 545     


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 
            550                 555                 560         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        565                 570                 575             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    580                 585                 590                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
595                 600                 605                 610 


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                615                 620                 625     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            630                 635                 640         


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

<220>
<223>  Fc cassette from pSYN-FIX-030

<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 cassette from pSYN-FIX-030


<220>
<221>  SIGNAL
<222>  (-20)..(-1)

<220>
<221>  mat_peptide
<222>  (1)..(227)

<400>  4

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
-20                 -15                 -10                 -5  


Gly Ser Thr Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
            -1  1               5                   10          


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        15                  20                  25              


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    30                  35                  40                  


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
45                  50                  55                  60  


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
                65                  70                  75      


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            80                  85                  90          


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
        95                  100                 105             


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    110                 115                 120                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
125                 130                 135                 140 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                145                 150                 155     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            160                 165                 170         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        175                 180                 185             


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
    190                 195                 200                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
205                 210                 215                 220 


Leu Ser Leu Ser Pro Gly Lys 
                225         


<210>  5
<211>  5052
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  B-Domain Deleted FVIIIFc

<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

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>  6
<211>  1684
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  B-Domain Deleted FVIIIFc


<220>
<221>  SIGNAL
<222>  (-19)..(-1)

<220>
<221>  mat_peptide
<222>  (1)..(1665)

<400>  6

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


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
        -1  1               5                   10              


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
    15                  20                  25                  


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
30                  35                  40                  45  


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


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
            65                  70                  75          


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
        80                  85                  90              


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
    95                  100                 105                 


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
110                 115                 120                 125 


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


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
            145                 150                 155         


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
        160                 165                 170             


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
    175                 180                 185                 


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
190                 195                 200                 205 


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


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


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
        240                 245                 250             


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
    255                 260                 265                 


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
270                 275                 280                 285 


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


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


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
        320                 325                 330             


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
    335                 340                 345                 


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
350                 355                 360                 365 


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


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
            385                 390                 395         


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
        400                 405                 410             


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
    415                 420                 425                 


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
430                 435                 440                 445 


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


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
            465                 470                 475         


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
        480                 485                 490             


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
    495                 500                 505                 


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
510                 515                 520                 525 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
                530                 535                 540     


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
        560                 565                 570             


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
    575                 580                 585                 


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
590                 595                 600                 605 


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


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
            625                 630                 635         


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
        640                 645                 650             


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
    655                 660                 665                 


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
670                 675                 680                 685 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
                690                 695                 700     


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
            705                 710                 715         


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
        720                 725                 730             


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
    735                 740                 745                 


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
750                 755                 760                 765 


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


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


Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
        800                 805                 810             


Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln 
    815                 820                 825                 


Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
830                 835                 840                 845 


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


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


Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
        880                 885                 890             


Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg 
    895                 900                 905                 


Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val 
910                 915                 920                 925 


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


Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
            945                 950                 955         


Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His 
        960                 965                 970             


Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe 
    975                 980                 985                 


Asp Glu Thr Lys Ser Trp Tyr Phe Thr Glu Asn  Met Glu Arg Asn Cys  
990                 995                 1000                 1005 


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


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


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


Leu Ser Met Gly Ser  Asn Glu Asn Ile His  Ser Ile His Phe Ser  
                1055                 1060                 1065 


Gly His Val Phe Thr  Val Arg Lys Lys Glu  Glu Tyr Lys Met Ala  
                1070                 1075                 1080 


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


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


His Leu His Ala Gly  Met Ser Thr Leu Phe  Leu Val Tyr Ser Asn  
                1115                 1120                 1125 


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


Phe Gln Ile Thr Ala  Ser Gly Gln Tyr Gly  Gln Trp Ala Pro Lys  
                1145                 1150                 1155 


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


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


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


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


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


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


Phe Asn Pro Pro Ile  Ile Ala Arg Tyr Ile  Arg Leu His Pro Thr  
                1250                 1255                 1260 


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


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


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


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


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


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


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


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


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


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


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


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


Thr His Thr Cys Pro  Pro Cys Pro Ala Pro  Glu Leu Leu Gly Gly  
                1445                 1450                 1455 


Pro Ser Val Phe Leu  Phe Pro Pro Lys Pro  Lys Asp Thr Leu Met  
                1460                 1465                 1470 


Ile Ser Arg Thr Pro  Glu Val Thr Cys Val  Val Val Asp Val Ser  
                1475                 1480                 1485 


His Glu Asp Pro Glu  Val Lys Phe Asn Trp  Tyr Val Asp Gly Val  
                1490                 1495                 1500 


Glu Val His Asn Ala  Lys Thr Lys Pro Arg  Glu Glu Gln Tyr Asn  
                1505                 1510                 1515 


Ser Thr Tyr Arg Val  Val Ser Val Leu Thr  Val Leu His Gln Asp  
                1520                 1525                 1530 


Trp Leu Asn Gly Lys  Glu Tyr Lys Cys Lys  Val Ser Asn Lys Ala  
                1535                 1540                 1545 


Leu Pro Ala Pro Ile  Glu Lys Thr Ile Ser  Lys Ala Lys Gly Gln  
                1550                 1555                 1560 


Pro Arg Glu Pro Gln  Val Tyr Thr Leu Pro  Pro Ser Arg Asp Glu  
                1565                 1570                 1575 


Leu Thr Lys Asn Gln  Val Ser Leu Thr Cys  Leu Val Lys Gly Phe  
                1580                 1585                 1590 


Tyr Pro Ser Asp Ile  Ala Val Glu Trp Glu  Ser Asn Gly Gln Pro  
                1595                 1600                 1605 


Glu Asn Asn Tyr Lys  Thr Thr Pro Pro Val  Leu Asp Ser Asp Gly  
                1610                 1615                 1620 


Ser Phe Phe Leu Tyr  Ser Lys Leu Thr Val  Asp Lys Ser Arg Trp  
                1625                 1630                 1635 


Gln Gln Gly Asn Val  Phe Ser Cys Ser Val  Met His Glu Ala Leu  
                1640                 1645                 1650 


His Asn His Tyr Thr  Gln Lys Ser Leu Ser  Leu Ser Pro Gly Lys  
                1655                 1660                 1665 


<210>  7
<211>  741
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fc Sequence

<400>  7
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>  8
<211>  247
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fc chain


<220>
<221>  SIGNAL
<222>  (-20)..(-1)

<220>
<221>  mat_peptide
<222>  (-1)..(227)

<400>  8

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
-20                 -15                 -10                 -5  


Gly Ser Thr Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
            -1  1               5                   10          


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        15                  20                  25              


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    30                  35                  40                  


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
45                  50                  55                  60  


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
                65                  70                  75      


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            80                  85                  90          


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
        95                  100                 105             


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    110                 115                 120                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
125                 130                 135                 140 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                145                 150                 155     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            160                 165                 170         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        175                 180                 185             


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
    190                 195                 200                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
205                 210                 215                 220 


Leu Ser Leu Ser Pro Gly Lys 
                225         


<210>  9
<211>  7734
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Full Length FVIIIFc

<400>  9
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>  10
<211>  2578
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Full Length FVIIIFc


<220>
<221>  SIGNAL
<222>  (-19)..(-1)

<220>
<221>  mat_peptide
<222>  (1)..(2559)

<400>  10

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


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
        -1  1               5                   10              


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
    15                  20                  25                  


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
30                  35                  40                  45  


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


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
            65                  70                  75          


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
        80                  85                  90              


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
    95                  100                 105                 


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
110                 115                 120                 125 


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


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
            145                 150                 155         


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
        160                 165                 170             


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
    175                 180                 185                 


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
190                 195                 200                 205 


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


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


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
        240                 245                 250             


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
    255                 260                 265                 


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
270                 275                 280                 285 


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


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


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
        320                 325                 330             


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
    335                 340                 345                 


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
350                 355                 360                 365 


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


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
            385                 390                 395         


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
        400                 405                 410             


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
    415                 420                 425                 


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
430                 435                 440                 445 


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


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
            465                 470                 475         


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
        480                 485                 490             


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
    495                 500                 505                 


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
510                 515                 520                 525 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
                530                 535                 540     


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
        560                 565                 570             


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
    575                 580                 585                 


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
590                 595                 600                 605 


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


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
            625                 630                 635         


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
        640                 645                 650             


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
    655                 660                 665                 


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
670                 675                 680                 685 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
                690                 695                 700     


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
            705                 710                 715         


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
        720                 725                 730             


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
    735                 740                 745                 


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
750                 755                 760                 765 


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


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
            785                 790                 795         


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
        800                 805                 810             


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
    815                 820                 825                 


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
830                 835                 840                 845 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
                850                 855                 860     


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
            865                 870                 875         


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
        880                 885                 890             


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
    895                 900                 905                 


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
910                 915                 920                 925 


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


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
            945                 950                 955         


Ser Ser Trp Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe 
        960                 965                 970             


Lys Gly Lys Arg Ala His Gly Pro Ala Leu Leu Thr Lys Asp Asn Ala 
    975                 980                 985                 


Leu Phe Lys Val Ser Ile Ser Leu Leu Lys Thr  Asn Lys Thr Ser Asn  
990                 995                 1000                 1005 


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


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


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


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


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


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


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


Arg Thr His Gly Lys  Asn Ser Leu Asn Ser  Gly Gln Gly Pro Ser  
                1115                 1120                 1125 


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


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


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


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


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


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


Thr Val Thr Gly Thr  Lys Asn Phe Met Lys  Asn Leu Phe Leu Leu  
                1220                 1225                 1230 


Ser Thr Arg Gln Asn  Val Glu Gly Ser Tyr  Asp Gly Ala Tyr Ala  
                1235                 1240                 1245 


Pro Val Leu Gln Asp  Phe Arg Ser Leu Asn  Asp Ser Thr Asn Arg  
                1250                 1255                 1260 


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


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


Tyr Ala Cys Thr Thr  Arg Ile Ser Pro Asn  Thr Ser Gln Gln Asn  
                1295                 1300                 1305 


Phe Val Thr Gln Arg  Ser Lys Arg Ala Leu  Lys Gln Phe Arg Leu  
                1310                 1315                 1320 


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


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


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


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


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


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


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


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


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


Gln Arg Glu Val Gly  Ser Leu Gly Thr Ser  Ala Thr Asn Ser Val  
                1460                 1465                 1470 


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


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


Tyr Gln Lys Asp Leu  Phe Pro Thr Glu Thr  Ser Asn Gly Ser Pro  
                1505                 1510                 1515 


Gly His Leu Asp Leu  Val Glu Gly Ser Leu  Leu Gln Gly Thr Glu  
                1520                 1525                 1530 


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


Phe Leu Arg Val Ala  Thr Glu Ser Ser Ala  Lys Thr Pro Ser Lys  
                1550                 1555                 1560 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Phe Thr Glu Asn Met  Glu Arg Asn Cys Arg  Ala Pro Cys Asn Ile  
                1895                 1900                 1905 


Gln Met Glu Asp Pro  Thr Phe Lys Glu Asn  Tyr Arg Phe His Ala  
                1910                 1915                 1920 


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


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


Glu Asn Ile His Ser  Ile His Phe Ser Gly  His Val Phe Thr Val  
                1955                 1960                 1965 


Arg Lys Lys Glu Glu  Tyr Lys Met Ala Leu  Tyr Asn Leu Tyr Pro  
                1970                 1975                 1980 


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


Trp Arg Val Glu Cys  Leu Ile Gly Glu His  Leu His Ala Gly Met  
                2000                 2005                 2010 


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


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


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


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


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


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


Phe Ile Ile Met Tyr  Ser Leu Asp Gly Lys  Lys Trp Gln Thr Tyr  
                2105                 2110                 2115 


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


Asp Ser Ser Gly Ile  Lys His Asn Ile Phe  Asn Pro Pro Ile Ile  
                2135                 2140                 2145 


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


Thr Leu Arg Met Glu  Leu Met Gly Cys Asp  Leu Asn Ser Cys Ser  
                2165                 2170                 2175 


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


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


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


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


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


Leu Leu Thr Ser Met  Tyr Val Lys Glu Phe  Leu Ile Ser Ser Ser  
                2255                 2260                 2265 


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


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


Ser Leu Asp Pro Pro  Leu Leu Thr Arg Tyr  Leu Arg Ile His Pro  
                2300                 2305                 2310 


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


Cys Glu Ala Gln Asp  Leu Tyr Asp Lys Thr  His Thr Cys Pro Pro  
                2330                 2335                 2340 


Cys Pro Ala Pro Glu  Leu Leu Gly Gly Pro  Ser Val Phe Leu Phe  
                2345                 2350                 2355 


Pro Pro Lys Pro Lys  Asp Thr Leu Met Ile  Ser Arg Thr Pro Glu  
                2360                 2365                 2370 


Val Thr Cys Val Val  Val Asp Val Ser His  Glu Asp Pro Glu Val  
                2375                 2380                 2385 


Lys Phe Asn Trp Tyr  Val Asp Gly Val Glu  Val His Asn Ala Lys  
                2390                 2395                 2400 


Thr Lys Pro Arg Glu  Glu Gln Tyr Asn Ser  Thr Tyr Arg Val Val  
                2405                 2410                 2415 


Ser Val Leu Thr Val  Leu His Gln Asp Trp  Leu Asn Gly Lys Glu  
                2420                 2425                 2430 


Tyr Lys Cys Lys Val  Ser Asn Lys Ala Leu  Pro Ala Pro Ile Glu  
                2435                 2440                 2445 


Lys Thr Ile Ser Lys  Ala Lys Gly Gln Pro  Arg Glu Pro Gln Val  
                2450                 2455                 2460 


Tyr Thr Leu Pro Pro  Ser Arg Asp Glu Leu  Thr Lys Asn Gln Val  
                2465                 2470                 2475 


Ser Leu Thr Cys Leu  Val Lys Gly Phe Tyr  Pro Ser Asp Ile Ala  
                2480                 2485                 2490 


Val Glu Trp Glu Ser  Asn Gly Gln Pro Glu  Asn Asn Tyr Lys Thr  
                2495                 2500                 2505 


Thr Pro Pro Val Leu  Asp Ser Asp Gly Ser  Phe Phe Leu Tyr Ser  
                2510                 2515                 2520 


Lys Leu Thr Val Asp  Lys Ser Arg Trp Gln  Gln Gly Asn Val Phe  
                2525                 2530                 2535 


Ser Cys Ser Val Met  His Glu Ala Leu His  Asn His Tyr Thr Gln  
                2540                 2545                 2550 


Lys Ser Leu Ser Leu  Ser Pro Gly Lys 
                2555                 


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

<220>
<223>  Partial  B domain

<400>  11

Ser Phe Ser Gln Asn Ser Arg His Pro Ser Gln Asn Pro Pro Val Leu 
1               5                   10                  15      


Lys Arg His Gln Arg 
            20      


<210>  12
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  albumin-binding peptide

<400>  12

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


<210>  13
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP peptide

<400>  13

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>  14
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTP peptide

<400>  14

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>  15
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  15

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

<220>
<223>  PAS peptide

<400>  16

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>  17
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  17

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>  18
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  18

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


Ser Pro Ser 
            


<210>  19
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  19

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>  20
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  20

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>  21
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PAS peptide

<400>  21

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  


