                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
       Netris Pharma
       Centre National de la Recherche Scientifique (CNRS)
       Universit Claude Bernard Lyon 1 (UCBL)
       Centre Leon Berard, Centre regional de lutte contre le cancer
 
<120>  Recombinant Fc-fusion protein of the fifth fibronectin type III domain of DCC

<130>  S1802 PCT S3

<150>  EP 10 29 0459.6
<151>  2010-08-26

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  1084
<212>  DNA
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: DNA encoding the 
       DCC-fusion protein (Fn5-Fc fusion protein) 7800"

<400>  1
aagcttgccg ccaccatggg atggagctgt atcatcctct tcttggtagc aacagctaca       60

ggtgtccact ccagcacccc catgctgcct ccagtgggcg tccaggccgt ggctctcaca      120

cacgacgcag tccgcgtgtc ctgggccgat aactctgttc ccaagaatca gaaaacctca      180

gaagtgagac tgtacactgt ccgctggcgg acatccttct ccgcttctgc aaagtataag      240

agtgaagaca ccactagcct ttcctacacc gccacagggc tgaaacctaa caccatgtat      300

gagttttctg tgatggtaac aaagaatagg agatcaagca cctggtccat gactgctcat      360

gcaacaacct acgaggccgc tccaaaatct tgtgacaaaa ctcacacatg tccaccgtgc      420

ccagcacctg aactcctggg gggaccgtca gtcttcctct tccccccaaa acccaaggac      480

accctcatga tctcccggac ccctgaggtc acgtgcgtgg tggtggacgt gagccacgaa      540

gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca      600

aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg      660

caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca      720

gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac      780

accctgcccc catcacggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc      840

aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac      900

aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag      960

ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat     1020

gaggctctgc acaaccacta cacgcagaag agcctctccc tgtccccggg caaatgagct     1080

agcg                                                                  1084


<210>  2
<211>  353
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       the DCC-fusion protein (Fn5-Fc fusion protein) 7800"

<400>  2

Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 
1               5                   10                  15      


Val His Ser Ser Thr Pro Met Leu Pro Pro Val Gly Val Gln Ala Val 
            20                  25                  30          


Ala Leu Thr His Asp Ala Val Arg Val Ser Trp Ala Asp Asn Ser Val 
        35                  40                  45              


Pro Lys Asn Gln Lys Thr Ser Glu Val Arg Leu Tyr Thr Val Arg Trp 
    50                  55                  60                  


Arg Thr Ser Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp Thr Thr 
65                  70                  75                  80  


Ser Leu Ser Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met Tyr Glu 
                85                  90                  95      


Phe Ser Val Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp Ser Met 
            100                 105                 110         


Thr Ala His Ala Thr Thr Tyr Glu Ala Ala Pro Lys Ser Cys Asp Lys 
        115                 120                 125             


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
    130                 135                 140                 


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
145                 150                 155                 160 


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
                165                 170                 175     


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
            180                 185                 190         


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
        195                 200                 205             


Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
    210                 215                 220                 


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
225                 230                 235                 240 


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
                245                 250                 255     


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
            260                 265                 270         


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
        275                 280                 285             


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
    290                 295                 300                 


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
305                 310                 315                 320 


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
                325                 330                 335     


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            340                 345                 350         


Lys 
    


<210>  3
<211>  334
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       mature DCC-fusion protein (Fn5-Fc fusion protein) 7800"

<400>  3

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


His Asp Ala Val Arg Val Ser Trp Ala Asp Asn Ser Val Pro Lys Asn 
            20                  25                  30          


Gln Lys Thr Ser Glu Val Arg Leu Tyr Thr Val Arg Trp Arg Thr Ser 
        35                  40                  45              


Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp Thr Thr Ser Leu Ser 
    50                  55                  60                  


Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met Tyr Glu Phe Ser Val 
65                  70                  75                  80  


Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp Ser Met Thr Ala His 
                85                  90                  95      


Ala Thr Thr Tyr Glu Ala Ala Pro Lys Ser Cys Asp Lys Thr His Thr 
            100                 105                 110         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        115                 120                 125             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    130                 135                 140                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
145                 150                 155                 160 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                165                 170                 175     


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
            180                 185                 190         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        195                 200                 205             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    210                 215                 220                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
225                 230                 235                 240 


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                245                 250                 255     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            260                 265                 270         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        275                 280                 285             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    290                 295                 300                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
305                 310                 315                 320 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330                 


<210>  4
<211>  334
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       mature Fn5-Fc fusion protein 7809"

<400>  4

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


His Asp Ala Val Arg Val Ser Trp Ala Asp Asn Ser Val Pro Lys Asn 
            20                  25                  30          


Gln Lys Thr Ser Glu Val Arg Leu Tyr Thr Val Arg Trp Arg Thr Ser 
        35                  40                  45              


Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp Thr Thr Ser Leu Ser 
    50                  55                  60                  


Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met Tyr Glu Phe Ser Val 
65                  70                  75                  80  


Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp Ser Met Thr Ala His 
                85                  90                  95      


Ala Thr Thr Tyr Glu Ala Ala Pro Lys Ser Ala Asp Lys Thr His Thr 
            100                 105                 110         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        115                 120                 125             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    130                 135                 140                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
145                 150                 155                 160 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                165                 170                 175     


Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
            180                 185                 190         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        195                 200                 205             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    210                 215                 220                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
225                 230                 235                 240 


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                245                 250                 255     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            260                 265                 270         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        275                 280                 285             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    290                 295                 300                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
305                 310                 315                 320 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330                 


<210>  5
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       mature Fn4-Fn5-Fc fusion protein 7801"

<400>  5

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


Cys Ile Ile Met Ser Trp Thr Pro Pro Leu Asn Pro Asn Ile Val Val 
            20                  25                  30          


Arg Gly Tyr Ile Ile Gly Tyr Gly Val Gly Ser Pro Tyr Ala Glu Thr 
        35                  40                  45              


Val Arg Val Asp Ser Lys Gln Arg Tyr Tyr Ser Ile Glu Arg Leu Glu 
    50                  55                  60                  


Ser Ser Ser His Tyr Val Ile Ser Leu Lys Ala Phe Asn Asn Ala Gly 
65                  70                  75                  80  


Glu Gly Val Pro Leu Tyr Glu Ser Ala Thr Thr Arg Ser Ile Thr Asp 
                85                  90                  95      


Pro Thr Asp Pro Val Asp Tyr Tyr Pro Leu Leu Asp Asp Phe Pro Thr 
            100                 105                 110         


Ser Val Pro Asp Leu Ser Thr Pro Met Leu Pro Pro Val Gly Val Gln 
        115                 120                 125             


Ala Val Ala Leu Thr His Asp Ala Val Arg Val Ser Trp Ala Asp Asn 
    130                 135                 140                 


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


Arg Trp Arg Thr Ser Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp 
                165                 170                 175     


Thr Thr Ser Leu Ser Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met 
            180                 185                 190         


Tyr Glu Phe Ser Val Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp 
        195                 200                 205             


Ser Met Thr Ala His Ala Thr Thr Tyr Glu Ala Ala Pro Lys Ser Cys 
    210                 215                 220                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                245                 250                 255     


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             


Pro Gly Lys 
    450     


<210>  6
<211>  333
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       mature Fn5-Fc fusion protein 7802"

<400>  6

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


His Asp Ala Val Arg Val Ser Trp Ala Asp Asn Ser Val Pro Lys Asn 
            20                  25                  30          


Gln Lys Thr Ser Glu Val Arg Leu Tyr Thr Val Arg Trp Arg Thr Ser 
        35                  40                  45              


Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp Thr Thr Ser Leu Ser 
    50                  55                  60                  


Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met Tyr Glu Phe Ser Val 
65                  70                  75                  80  


Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp Ser Gly Gly Gly Gly 
                85                  90                  95      


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Asp Lys Thr His Thr Cys 
            100                 105                 110         


Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 
        115                 120                 125             


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
    130                 135                 140                 


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
145                 150                 155                 160 


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
                165                 170                 175     


Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
            180                 185                 190         


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
        195                 200                 205             


Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
    210                 215                 220                 


Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
225                 230                 235                 240 


Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 
                245                 250                 255     


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
            260                 265                 270         


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
        275                 280                 285             


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
    290                 295                 300                 


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
305                 310                 315                 320 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330             


<210>  7
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<221>  Source
<223>  /Note="Description of Artificial Sequence: Amino acid sequence of
       mature Fn4-Fn5-Fc fusion protein 7803"

<400>  7

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


Cys Ile Ile Met Ser Trp Thr Pro Pro Leu Asn Pro Asn Ile Val Val 
            20                  25                  30          


Arg Gly Tyr Ile Ile Gly Tyr Gly Val Gly Ser Pro Tyr Ala Glu Thr 
        35                  40                  45              


Val Arg Val Asp Ser Lys Gln Arg Tyr Tyr Ser Ile Glu Arg Leu Glu 
    50                  55                  60                  


Ser Ser Ser His Tyr Val Ile Ser Leu Lys Ala Phe Asn Asn Ala Gly 
65                  70                  75                  80  


Glu Gly Val Pro Leu Tyr Glu Ser Ala Thr Thr Arg Ser Ile Thr Asp 
                85                  90                  95      


Pro Thr Asp Pro Val Asp Tyr Tyr Pro Leu Leu Asp Asp Phe Pro Thr 
            100                 105                 110         


Ser Val Pro Asp Leu Ser Thr Pro Met Leu Pro Pro Val Gly Val Gln 
        115                 120                 125             


Ala Val Ala Leu Thr His Asp Ala Val Arg Val Ser Trp Ala Asp Asn 
    130                 135                 140                 


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


Arg Trp Arg Thr Ser Phe Ser Ala Ser Ala Lys Tyr Lys Ser Glu Asp 
                165                 170                 175     


Thr Thr Ser Leu Ser Tyr Thr Ala Thr Gly Leu Lys Pro Asn Thr Met 
            180                 185                 190         


Tyr Glu Phe Ser Val Met Val Thr Lys Asn Arg Arg Ser Ser Thr Trp 
        195                 200                 205             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


