                         SEQUENCE LISTING

<110>  Oxford University Innovation Limited
 
<120>  CHIMAERIC PROTEINS AND THERAPEUTIC AGENTS

<130>  P286556WO

<160>  41    

<170>  PatentIn version 3.5

<210>  1
<211>  188
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


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


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Glu Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Pro Ser Arg Thr Val Asp Thr Lys 
        115                 120                 125             


Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Phe Ile Glu Thr 
    130                 135                 140                 


Ser Ala Lys Thr Arg Gln Gly Val Asp Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Lys His Lys Glu Lys Met Ser Lys Asp Gly Lys Lys 
                165                 170                 175     


Lys Lys Lys Lys Ser Lys Thr Lys Cys Val Ile Met 
            180                 185             


<210>  2
<211>  189
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


Val Phe Ala Ile Asn Asn Thr Lys Ser Phe Glu Asp Ile His Gln Tyr 
                85                  90                  95      


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Asp Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Ala Ala Arg Thr Val Glu Ser Arg 
        115                 120                 125             


Gln Ala Gln Asp Leu Ala Arg Ser Tyr Gly Ile Pro Tyr Ile Glu Thr 
    130                 135                 140                 


Ser Ala Lys Thr Arg Gln Gly Val Glu Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Gln His Lys Leu Arg Lys Leu Asn Pro Pro Asp Glu 
                165                 170                 175     


Ser Gly Pro Gly Cys Met Ser Cys Lys Cys Val Leu Ser 
            180                 185                 


<210>  3
<211>  189
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Gly Gly Val Gly Lys 
1               5                   10                  15      


Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr 
            20                  25                  30          


Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly 
        35                  40                  45              


Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu Glu Tyr 
    50                  55                  60                  


Ser Ala Met Arg Asp Gln Tyr Met Arg Thr Gly Glu Gly Phe Leu Cys 
65                  70                  75                  80  


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


Arg Glu Gln Ile Lys Arg Val Lys Asp Ser Asp Asp Val Pro Met Val 
            100                 105                 110         


Leu Val Gly Asn Lys Cys Asp Leu Pro Thr Arg Thr Val Asp Thr Lys 
        115                 120                 125             


Gln Ala His Glu Leu Ala Lys Ser Tyr Gly Ile Pro Phe Ile Glu Thr 
    130                 135                 140                 


Ser Ala Lys Thr Arg Gln Gly Val Glu Asp Ala Phe Tyr Thr Leu Val 
145                 150                 155                 160 


Arg Glu Ile Arg Gln Tyr Arg Met Lys Lys Leu Asn Ser Ser Asp Asp 
                165                 170                 175     


Gly Thr Gln Gly Cys Met Gly Leu Pro Cys Val Val Met 
            180                 185                 


<210>  4
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-pan RAS intracellular single domain antibody iDAb RAS

<400>  4

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 
            20                  25                  30          


Thr Phe Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu 
        35                  40                  45              


Trp Val Ser Tyr Ile Ser Arg Thr Ser Lys Thr Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


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


Val Thr Val Ser Ser 
        115         


<210>  5
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimaeric protein UBOX-iDAb RAS

<400>  5

Met Arg Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala 
1               5                   10                  15      


Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu 
            20                  25                  30          


Ser Glu Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu 
        35                  40                  45              


Arg Glu Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp 
    50                  55                  60                  


Ser His Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys 
65                  70                  75                  80  


Tyr Met Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg 
                85                  90                  95      


Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu 
            100                 105                 110         


Leu Met Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg 
        115                 120                 125             


Lys Asp Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val 
    130                 135                 140                 


Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met 
145                 150                 155                 160 


Lys Glu Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp 
                165                 170                 175     


Tyr Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Met Asp Tyr Lys Asp 
            180                 185                 190         


Asp Asp Asp Lys Thr Ser Met Ala Glu Val Gln Leu Leu Glu Ser Gly 
        195                 200                 205             


Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
    210                 215                 220                 


Ser Gly Phe Thr Phe Ser Thr Phe Ser Met Asn Trp Val Arg Gln Ala 
225                 230                 235                 240 


Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Ser Arg Thr Ser Lys 
                245                 250                 255     


Thr Ile Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
            260                 265                 270         


Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala 
        275                 280                 285             


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Arg Phe Phe Asp Tyr 
    290                 295                 300                 


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


Asp Glu Ser Gly Pro Gly Cys Met Ser Cys Lys Cys Val Leu Ser 
                325                 330                 335 


<210>  6
<211>  157
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-KRAS DARPin K19

<400>  6

Met Asp Leu Gly Lys Lys Leu Leu Glu Ala Ala Arg Ala Gly Gln Asp 
1               5                   10                  15      


Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala Ser 
            20                  25                  30          


Asp Arg Trp Gly Trp Thr Pro Leu His Leu Ala Ala Trp Trp Gly His 
        35                  40                  45              


Leu Glu Ile Val Glu Val Leu Leu Lys Arg Gly Ala Asp Val Ser Ala 
    50                  55                  60                  


Ala Asp Leu His Gly Gln Ser Pro Leu His Leu Ala Ala Met Val Gly 
65                  70                  75                  80  


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn 
                85                  90                  95      


Ala Lys Asp Thr Met Gly Ala Thr Pro Leu His Leu Ala Ala Arg Ser 
            100                 105                 110         


Gly His Leu Glu Ile Val Glu Glu Leu Leu Lys Asn Gly Ala Asp Met 
        115                 120                 125             


Asn Ala Gln Asp Lys Phe Gly Lys Thr Thr Phe Asp Ile Ser Thr Asp 
    130                 135                 140                 


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Leu 
145                 150                 155         


<210>  7
<211>  471
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA encoding DARPin K19

<400>  7
atggatctgg gaaaaaaact gctggaagcc gcgcgtgccg ggcaggacga tgaggtccgt       60

attcttatgg cgaatggtgc agatgttaac gcgagcgatc gttggggttg gacgccgctg      120

cacctggcag cgtggtgggg tcacctcgaa attgtggaag tgctgttgaa gcgcggtgca      180

gatgttagcg cggcagatct gcacggtcaa tcgccgctgc atctggcagc gatggtcggc      240

cacctcgaaa ttgtggaagt gctgttgaag tacggtgcag atgttaacgc gaaagatacg      300

atgggtgcaa cgccgctgca cctggcagcg cgaagcggtc acctcgaaat tgtggaagag      360

ctgttgaaga acggtgcaga tatgaatgct caggataagt ttggcaaaac cacgtttgat      420

atctccactg ataatggcaa cgaagattta gcggaaatcc tgcagaaact g               471


<210>  8
<211>  157
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of anti-KRAS DARPin K13

<400>  8

Met Asp Leu Gly Lys Lys Leu Leu Glu Ala Ala Arg Ala Gly Gln Asp 
1               5                   10                  15      


Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala Ser 
            20                  25                  30          


Asp Arg Trp Gly Trp Thr Pro Leu His Leu Ala Ala Trp Trp Gly His 
        35                  40                  45              


Leu Glu Ile Val Glu Val Leu Leu Lys His Gly Ala Asp Val Asn Ala 
    50                  55                  60                  


Ala Asp Leu His Gly Gln Thr Pro Leu His Leu Ala Ala Met Val Gly 
65                  70                  75                  80  


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn 
                85                  90                  95      


Ala Lys Asp Thr Met Gly Ala Thr Pro Leu His Leu Ala Ala Gln Ser 
            100                 105                 110         


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp Val 
        115                 120                 125             


Asn Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile Asp 
    130                 135                 140                 


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Leu 
145                 150                 155         


<210>  9
<211>  471
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA encoding K13

<400>  9
atggatctgg gaaaaaaact gctggaagcc gcgcgtgccg gacaggacga tgaggtccgt       60

attcttatgg cgaacggtgc agatgttaac gcgagcgatc gctggggttg gacgccgctg      120

catctggcag cgtggtgggg tcacctcgaa attgtggaag tgctgttgaa gcacggtgca      180

gatgttaacg cggcagatct gcacggtcaa acgccgctgc atctggcagc gatggtcggt      240

cacctcgaaa ttgtggaagt gctgttgaag tacggtgcag atgttaacgc gaaagatacg      300

atgggtgcaa cgccgctgca tctggcagcg caaagcggtc acctcgaaat tgtggaagtg      360

ctgttgaaga acggtgcaga tgtgaatgct caggataagt ttggcaaaac cgcgtttgat      420

atctccattg ataatggcaa cgaagattta gcggaaatcc tgcagaaact g               471


<210>  10
<211>  281
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-KRAS scFv P2-E2

<400>  10

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 
            20                  25                  30          


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


Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Asp Tyr Gly Asp Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Val Met Thr Gln 
    130                 135                 140                 


Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 
145                 150                 155                 160 


Cys Arg Ala Ser Gln Thr Val Ser Thr Tyr Leu Ala Trp Tyr Gln Gln 
                165                 170                 175     


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Leu 
            180                 185                 190         


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
        195                 200                 205             


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Ala Ala Val Tyr 
    210                 215                 220                 


Tyr Cys Gln Gln Tyr Gly Ser Ser Val Ile Thr Phe Gly Gln Gly Thr 
225                 230                 235                 240 


Lys Leu Glu Ile Lys Arg Ala Ala Ala Ser Ala His His His His His 
                245                 250                 255     


His Lys Leu Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp 
            260                 265                 270         


Ile Asp Tyr Lys Asp Asp Asp Asp Lys 
        275                 280     


<210>  11
<211>  289
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-KRAS scFv P2-F3

<400>  11

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


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


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


Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln 
    50                  55                  60                  


Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr 
65                  70                  75                  80  


Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Gly Ser Ser Trp Tyr Val Ala Phe Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Gln Met 
    130                 135                 140                 


Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr 
145                 150                 155                 160 


Ile Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Lys Tyr Asn Asn Lys 
                165                 170                 175     


Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu 
            180                 185                 190         


Ile Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe 
        195                 200                 205             


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
    210                 215                 220                 


Gln Pro Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Thr Thr 
225                 230                 235                 240 


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


Ala Ser Ala His His His His His His Lys Leu Asp Tyr Lys Asp His 
            260                 265                 270         


Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp 
        275                 280                 285             


Lys 
    


<210>  12
<211>  158
<212>  PRT
<213>  Homo sapiens

<400>  12

Met Ser Ser Ala Ile Glu Arg Lys Ser Leu Asp Pro Ser Glu Glu Pro 
1               5                   10                  15      


Val Asp Glu Val Leu Gln Ile Pro Pro Ser Leu Leu Thr Cys Gly Gly 
            20                  25                  30          


Cys Gln Gln Asn Ile Gly Asp Arg Tyr Phe Leu Lys Ala Ile Asp Gln 
        35                  40                  45              


Tyr Trp His Glu Asp Cys Leu Ser Cys Asp Leu Cys Gly Cys Arg Leu 
    50                  55                  60                  


Gly Glu Val Gly Arg Arg Leu Tyr Tyr Lys Leu Gly Arg Lys Leu Cys 
65                  70                  75                  80  


Arg Arg Asp Tyr Leu Arg Leu Phe Gly Gln Asp Gly Leu Cys Ala Ser 
                85                  90                  95      


Cys Asp Lys Arg Ile Arg Ala Tyr Glu Met Thr Met Arg Val Lys Asp 
            100                 105                 110         


Lys Val Tyr His Leu Glu Cys Phe Lys Cys Ala Ala Cys Gln Lys His 
        115                 120                 125             


Phe Cys Val Gly Asp Arg Tyr Leu Leu Ile Asn Ser Asp Ile Val Cys 
    130                 135                 140                 


Glu Gln Asp Ile Tyr Glu Trp Thr Lys Ile Asn Gly Met Ile 
145                 150                 155             


<210>  13
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-LMO2 VH576

<400>  13

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser 
            20                  25                  30          


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


Trp Val Ser Tyr Ile Ser Tyr Asn Ser Ser Ser Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Gly Leu Thr Glu Ser Leu Glu Leu Thr Ala Asp Trp 
            100                 105                 110         


Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  14
<211>  376
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-VH576, an exemplary chimaeric protein 
       of the second aspect of the invention

<400>  14

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly 
    210                 215                 220                 


Ser Gly Gly Gly Gly Ser Ala Ala Arg Met Ala Glu Val Gln Leu Leu 
225                 230                 235                 240 


Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
                245                 250                 255     


Cys Ala Ala Ser Gly Phe Ser Phe Ser His Ser Pro Met Asn Trp Val 
            260                 265                 270         


Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Ser Tyr 
        275                 280                 285             


Asn Ser Ser Ser Ile Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 
    290                 295                 300                 


Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 
305                 310                 315                 320 


Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Leu Thr 
                325                 330                 335     


Glu Ser Leu Glu Leu Thr Ala Asp Trp Phe Asp Tyr Trp Gly Gln Gly 
            340                 345                 350         


Thr Leu Val Thr Val Ser Ser Ala Ala Ala Glu Gln Lys Leu Ile Ser 
        355                 360                 365             


Glu Glu Asp Leu Asn Gly Ala Ala 
    370                 375     


<210>  15
<211>  213
<212>  PRT
<213>  Homo sapiens

<400>  15

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp 
    210             


<210>  16
<211>  639
<212>  DNA
<213>  Homo sapiens

<400>  16
atgccccgga gggcggagaa ctgggacgag gccgaggtag gcgcggagga ggcaggcgtc       60

gaagagtacg gccctgaaga agacggcggg gaggagtcgg gcgccgagga gtccggcccg      120

gaagagtccg gcccggagga actgggcgcc gaggaggaga tggaggccgg gcggccgcgg      180

cccgtgctgc gctcggtgaa ctcgcgcgag ccctcccagg tcatcttctg caatcgcagt      240

ccgcgcgtcg tgctgccagt atggctcaac ttcgacggcg agccgcagcc ctacccaacg      300

ctgccgcctg gcacgggccg ccgcatccac agctaccgag gtcacctttg gctcttcaga      360

gatgcaggga cacacgatgg gcttctggtt aaccaaactg aattatttgt gccatctctc      420

aatgttgacg gacagcctat ttttgccaat atcacactgc cagtgtatac tctgaaagag      480

cgatgcctcc aggttgtccg gagcctagtc aagcctgaga attacaggag actggacatc      540

gtcaggtcgc tctacgaaga tctggaagac cacccaaatg tgcagaaaga cctggagcgg      600

ctgacacagg agcgcattgc acatcaacgg atgggagat                             639


<210>  17
<211>  177
<212>  PRT
<213>  Homo sapiens

<400>  17

Met Arg Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala 
1               5                   10                  15      


Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu 
            20                  25                  30          


Ser Glu Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu 
        35                  40                  45              


Arg Glu Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp 
    50                  55                  60                  


Ser His Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys 
65                  70                  75                  80  


Tyr Met Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg 
                85                  90                  95      


Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu 
            100                 105                 110         


Leu Met Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg 
        115                 120                 125             


Lys Asp Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val 
    130                 135                 140                 


Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met 
145                 150                 155                 160 


Lys Glu Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp 
                165                 170                 175     


Tyr 
    


<210>  18
<211>  531
<212>  DNA
<213>  Homo sapiens

<400>  18
atgcggctga acttcgggga cgacatcccc agcgctcttc gaatcgcgaa gaagaagcgc       60

tggaacagca ttgaggagcg gcgcatccac caggagagcg agctgcactc ctacctctcc      120

aggctcattg ccgcggagcg tgagagggag ctggaagagt gccagcgaaa ccacgagggt      180

gatgaggacg acagccacgt ccgggcccag caggcctgca ttgaggccaa gcacgacaag      240

tacatggcgg acatggacga gcttttttct caggtggatg agaagaggaa gaagcgagac      300

atccccgact acctgtgtgg caagatcagc tttgagctga tgcgggagcc gtgcatcacg      360

cccagtggca tcacctacga ccgcaaggac atcgaggagc acctgcagcg tgtgggtcat      420

tttgaccccg tgacccggag ccccctgacc caggaacagc tcatccccaa cttggctatg      480

aaggaggtta ttgacgcatt catctctgag aatggctggg tggaggacta c               531


<210>  19
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of the linker sequence within VHL-DP-KRAS

<400>  19

Gly Gly Gly Gly Ser 
1               5   


<210>  20
<211>  393
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-DP KRAS (also referred to as VHL-K19),
       an exemplary chimaeric protein of the first aspect of the 
       invention

<400>  20

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Met 
    210                 215                 220                 


Asp Leu Gly Lys Lys Leu Leu Glu Ala Ala Arg Ala Gly Gln Asp Asp 
225                 230                 235                 240 


Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala Ser Asp 
                245                 250                 255     


Arg Trp Gly Trp Thr Pro Leu His Leu Ala Ala Trp Trp Gly His Leu 
            260                 265                 270         


Glu Ile Val Glu Val Leu Leu Lys Arg Gly Ala Asp Val Ser Ala Ala 
        275                 280                 285             


Asp Leu His Gly Gln Ser Pro Leu His Leu Ala Ala Met Val Gly His 
    290                 295                 300                 


Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn Ala 
305                 310                 315                 320 


Lys Asp Thr Met Gly Ala Thr Pro Leu His Leu Ala Ala Arg Ser Gly 
                325                 330                 335     


His Leu Glu Ile Val Glu Glu Leu Leu Lys Asn Gly Ala Asp Met Asn 
            340                 345                 350         


Ala Gln Asp Lys Phe Gly Lys Thr Thr Phe Asp Ile Ser Thr Asp Asn 
        355                 360                 365             


Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Leu Val Asp Gly Gly 
    370                 375                 380                 


Ser Asp Tyr Lys Asp Asp Asp Asp Lys 
385                 390             


<210>  21
<211>  1182
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence encoding protein VHL-DP KRAS

<400>  21
atgccccgga gggcggagaa ctgggacgag gccgaggtag gcgcggagga ggcaggcgtc       60

gaagagtacg gccctgaaga agacggcggg gaggagtcgg gcgccgagga gtccggcccg      120

gaagagtccg gcccggagga actgggcgcc gaggaggaga tggaggccgg gcggccgcgg      180

cccgtgctgc gctcggtgaa ctcgcgcgag ccctcccagg tcatcttctg caatcgcagt      240

ccgcgcgtcg tgctgccagt atggctcaac ttcgacggcg agccgcagcc ctacccaacg      300

ctgccgcctg gcacgggccg ccgcatccac agctaccgag gtcacctttg gctcttcaga      360

gatgcaggga cacacgatgg gcttctggtt aaccaaactg aattatttgt gccatctctc      420

aatgttgacg gacagcctat ttttgccaat atcacactgc cagtgtatac tctgaaagag      480

cgatgcctcc aggttgtccg gagcctagtc aagcctgaga attacaggag actggacatc      540

gtcaggtcgc tctacgaaga tctggaagac cacccaaatg tgcagaaaga cctggagcgg      600

ctgacacagg agcgcattgc acatcaacgg atgggagatc tcgagggcgg aggcggatct      660

gcggccgcaa tggatctggg aaaaaaactg ctggaagccg cgcgtgccgg gcaggacgat      720

gaggtccgta ttcttatggc gaatggtgca gatgttaacg cgagcgatcg ttggggttgg      780

acgccgctgc acctggcagc gtggtggggt cacctcgaaa ttgtggaagt gctgttgaag      840

cgcggtgcag atgttagcgc ggcagatctg cacggtcaat cgccgctgca tctggcagcg      900

atggtcggcc acctcgaaat tgtggaagtg ctgttgaagt acggtgcaga tgttaacgcg      960

aaagatacga tgggtgcaac gccgctgcac ctggcagcgc gaagcggtca cctcgaaatt     1020

gtggaagagc tgttgaagaa cggtgcagat atgaatgctc aggataagtt tggcaaaacc     1080

acgtttgata tctccactga taatggcaac gaagatttag cggaaatcct gcagaaactg     1140

gtcgacggcg ggtctgacta caaagacgac gatgacaagt aa                        1182


<210>  22
<211>  393
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-K13, an exemplary chimaeric protein of
       the first aspect of the invention

<400>  22

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Met 
    210                 215                 220                 


Asp Leu Gly Lys Lys Leu Leu Glu Ala Ala Arg Ala Gly Gln Asp Asp 
225                 230                 235                 240 


Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala Ser Asp 
                245                 250                 255     


Arg Trp Gly Trp Thr Pro Leu His Leu Ala Ala Trp Trp Gly His Leu 
            260                 265                 270         


Glu Ile Val Glu Val Leu Leu Lys His Gly Ala Asp Val Asn Ala Ala 
        275                 280                 285             


Asp Leu His Gly Gln Thr Pro Leu His Leu Ala Ala Met Val Gly His 
    290                 295                 300                 


Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn Ala 
305                 310                 315                 320 


Lys Asp Thr Met Gly Ala Thr Pro Leu His Leu Ala Ala Gln Ser Gly 
                325                 330                 335     


His Leu Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp Val Asn 
            340                 345                 350         


Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile Asp Asn 
        355                 360                 365             


Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Leu Val Asp Gly Gly 
    370                 375                 380                 


Ser Asp Tyr Lys Asp Asp Asp Asp Lys 
385                 390             


<210>  23
<211>  1182
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence encoding VHL-K13

<400>  23
atgccccgga gggcggagaa ctgggacgag gccgaggtag gcgcggagga ggcaggcgtc       60

gaagagtacg gccctgaaga agacggcggg gaggagtcgg gcgccgagga gtccggcccg      120

gaagagtccg gcccggagga actgggcgcc gaggaggaga tggaggccgg gcggccgcgg      180

cccgtgctgc gctcggtgaa ctcgcgcgag ccctcccagg tcatcttctg caatcgcagt      240

ccgcgcgtcg tgctgccagt atggctcaac ttcgacggcg agccgcagcc ctacccaacg      300

ctgccgcctg gcacgggccg ccgcatccac agctaccgag gtcacctttg gctcttcaga      360

gatgcaggga cacacgatgg gcttctggtt aaccaaactg aattatttgt gccatctctc      420

aatgttgacg gacagcctat ttttgccaat atcacactgc cagtgtatac tctgaaagag      480

cgatgcctcc aggttgtccg gagcctagtc aagcctgaga attacaggag actggacatc      540

gtcaggtcgc tctacgaaga tctggaagac cacccaaatg tgcagaaaga cctggagcgg      600

ctgacacagg agcgcattgc acatcaacgg atgggagatc tcgagggcgg aggcggatct      660

gcggccgcaa tggatctggg aaaaaaactg ctggaagccg cgcgtgccgg acaggacgat      720

gaggtccgta ttcttatggc gaacggtgca gatgttaacg cgagcgatcg ctggggttgg      780

acgccgctgc atctggcagc gtggtggggt cacctcgaaa ttgtggaagt gctgttgaag      840

cacggtgcag atgttaacgc ggcagatctg cacggtcaaa cgccgctgca tctggcagcg      900

atggtcggtc acctcgaaat tgtggaagtg ctgttgaagt acggtgcaga tgttaacgcg      960

aaagatacga tgggtgcaac gccgctgcat ctggcagcgc aaagcggtca cctcgaaatt     1020

gtggaagtgc tgttgaagaa cggtgcagat gtgaatgctc aggataagtt tggcaaaacc     1080

gcgtttgata tctccattga taatggcaac gaagatttag cggaaatcct gcagaaactg     1140

gtcgacggcg ggtctgacta caaagacgac gatgacaagt aa                        1182


<210>  24
<211>  357
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of UBOX-DP-KRAS, an exemplary chimaeric 
       protein of the first aspect of the invention

<400>  24

Met Arg Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala 
1               5                   10                  15      


Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu 
            20                  25                  30          


Ser Glu Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu 
        35                  40                  45              


Arg Glu Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp 
    50                  55                  60                  


Ser His Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys 
65                  70                  75                  80  


Tyr Met Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg 
                85                  90                  95      


Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu 
            100                 105                 110         


Leu Met Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg 
        115                 120                 125             


Lys Asp Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val 
    130                 135                 140                 


Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met 
145                 150                 155                 160 


Lys Glu Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp 
                165                 170                 175     


Tyr Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Met Asp Leu Gly Lys 
            180                 185                 190         


Lys Leu Leu Glu Ala Ala Arg Ala Gly Gln Asp Asp Glu Val Arg Ile 
        195                 200                 205             


Leu Met Ala Asn Gly Ala Asp Val Asn Ala Ser Asp Arg Trp Gly Trp 
    210                 215                 220                 


Thr Pro Leu His Leu Ala Ala Trp Trp Gly His Leu Glu Ile Val Glu 
225                 230                 235                 240 


Val Leu Leu Lys Arg Gly Ala Asp Val Ser Ala Ala Asp Leu His Gly 
                245                 250                 255     


Gln Ser Pro Leu His Leu Ala Ala Met Val Gly His Leu Glu Ile Val 
            260                 265                 270         


Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn Ala Lys Asp Thr Met 
        275                 280                 285             


Gly Ala Thr Pro Leu His Leu Ala Ala Arg Ser Gly His Leu Glu Ile 
    290                 295                 300                 


Val Glu Glu Leu Leu Lys Asn Gly Ala Asp Met Asn Ala Gln Asp Lys 
305                 310                 315                 320 


Phe Gly Lys Thr Thr Phe Asp Ile Ser Thr Asp Asn Gly Asn Glu Asp 
                325                 330                 335     


Leu Ala Glu Ile Leu Gln Lys Leu Val Asp Gly Gly Ser Asp Tyr Lys 
            340                 345                 350         


Asp Asp Asp Asp Lys 
        355         


<210>  25
<211>  1071
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence encoding UBOX-DP-KRAS

<400>  25
atgcggctga acttcgggga cgacatcccc agcgctcttc gaatcgcgaa gaagaagcgc       60

tggaacagca ttgaggagcg gcgcatccac caggagagcg agctgcactc ctacctctcc      120

aggctcattg ccgcggagcg tgagagggag ctggaagagt gccagcgaaa ccacgagggt      180

gatgaggacg acagccacgt ccgggcccag caggcctgca ttgaggccaa gcacgacaag      240

tacatggcgg acatggacga gcttttttct caggtggatg agaagaggaa gaagcgagac      300

atccccgact acctgtgtgg caagatcagc tttgagctga tgcgggagcc gtgcatcacg      360

cccagtggca tcacctacga ccgcaaggac atcgaggagc acctgcagcg tgtgggtcat      420

tttgaccccg tgacccggag ccccctgacc caggaacagc tcatccccaa cttggctatg      480

aaggaggtta ttgacgcatt catctctgag aatggctggg tggaggacta cctcgagggc      540

ggaggcggat ctgcggccgc aatggatctg ggaaaaaaac tgctggaagc cgcgcgtgcc      600

gggcaggacg atgaggtccg tattcttatg gcgaatggtg cagatgttaa cgcgagcgat      660

cgttggggtt ggacgccgct gcacctggca gcgtggtggg gtcacctcga aattgtggaa      720

gtgctgttga agcgcggtgc agatgttagc gcggcagatc tgcacggtca atcgccgctg      780

catctggcag cgatggtcgg ccacctcgaa attgtggaag tgctgttgaa gtacggtgca      840

gatgttaacg cgaaagatac gatgggtgca acgccgctgc acctggcagc gcgaagcggt      900

cacctcgaaa ttgtggaaga gctgttgaag aacggtgcag atatgaatgc tcaggataag      960

tttggcaaaa ccacgtttga tatctccact gataatggca acgaagattt agcggaaatc     1020

ctgcagaaac tggtcgacgg cgggtctgac tacaaagacg acgatgacaa g              1071


<210>  26
<211>  484
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-P2-E2, an exemplary chimaeric protein 
       of the first aspect of the invention

<400>  26

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    210                 215                 220                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Ala Glu Val Gln Leu Leu 
225                 230                 235                 240 


Glu Ser Gly Gly Gly Ser Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
                245                 250                 255     


Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val 
            260                 265                 270         


Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly 
        275                 280                 285             


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


Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 
305                 310                 315                 320 


Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Asp 
                325                 330                 335     


Tyr Gly Asp Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
            340                 345                 350         


Ser Ser Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        355                 360                 365             


Gly Ala Ser Asp Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val 
385                 390                 395                 400 


Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg 
                405                 410                 415     


Leu Leu Ile Tyr Gly Ala Ser Ser Leu Ala Thr Gly Ile Pro Asp Arg 
            420                 425                 430         


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg 
        435                 440                 445             


Leu Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser 
    450                 455                 460                 


Ser Val Ile Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ala 
465                 470                 475                 480 


Ala Ala Ser Ala 
                


<210>  27
<211>  492
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-P2-F3, an exemplary chimaeric protein 
       of the first aspect of the invention

<400>  27

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    210                 215                 220                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Ala Glu Val Gln Leu Val 
225                 230                 235                 240 


Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser 
                245                 250                 255     


Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val 
            260                 265                 270         


Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro 
        275                 280                 285             


Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr 
    290                 295                 300                 


Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg 
305                 310                 315                 320 


Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Gly 
                325                 330                 335     


Ser Ser Trp Tyr Val Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            340                 345                 350         


Thr Val Ser Ser Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             


Gly Gly Gly Ala Ser Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu 
    370                 375                 380                 


Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Ser Cys Lys Ser Ser Gln 
385                 390                 395                 400 


Ser Val Leu Tyr Lys Tyr Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln 
                405                 410                 415     


Gln Lys Pro Gly Gln Pro Pro Lys Leu Ile Ile Tyr Trp Ala Ser Thr 
            420                 425                 430         


Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 
        435                 440                 445             


Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Val 
    450                 455                 460                 


Tyr Tyr Cys Gln Gln Tyr Tyr Thr Thr Pro Tyr Thr Phe Gly Gln Gly 
465                 470                 475                 480 


Thr Lys Val Glu Ile Lys Arg Ala Ala Ala Ser Ala 
                485                 490         


<210>  28
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of UBOX-P2-E2, an exemplary chimaeric protein
       of the first aspect of the invention

<400>  28

Met Arg Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala 
1               5                   10                  15      


Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu 
            20                  25                  30          


Ser Glu Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu 
        35                  40                  45              


Arg Glu Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp 
    50                  55                  60                  


Ser His Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys 
65                  70                  75                  80  


Tyr Met Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg 
                85                  90                  95      


Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu 
            100                 105                 110         


Leu Met Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg 
        115                 120                 125             


Lys Asp Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val 
    130                 135                 140                 


Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met 
145                 150                 155                 160 


Lys Glu Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp 
                165                 170                 175     


Tyr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            180                 185                 190         


Gly Gly Gly Gly Ser Met Ala Glu Val Gln Leu Leu Glu Ser Gly Gly 
        195                 200                 205             


Gly Ser Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 
    210                 215                 220                 


Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro 
225                 230                 235                 240 


Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser 
                245                 250                 255     


Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 
            260                 265                 270         


Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
        275                 280                 285             


Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Asp Tyr Gly Asp Tyr 
    290                 295                 300                 


Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu 
305                 310                 315                 320 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp 
                325                 330                 335     


Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu 
            340                 345                 350         


Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Thr Val Ser Thr Tyr Leu 
        355                 360                 365             


Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr 
    370                 375                 380                 


Gly Ala Ser Ser Leu Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser 
385                 390                 395                 400 


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu 
                405                 410                 415     


Asp Ala Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Val Ile Thr 
            420                 425                 430         


Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala Ser Ala 
        435                 440                 445             


<210>  29
<211>  456
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of UBOX-P2-F3, an exemplary chimaeric protein
       of the first aspect of the invention

<400>  29

Met Arg Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala 
1               5                   10                  15      


Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu 
            20                  25                  30          


Ser Glu Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu 
        35                  40                  45              


Arg Glu Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp 
    50                  55                  60                  


Ser His Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys 
65                  70                  75                  80  


Tyr Met Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg 
                85                  90                  95      


Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu 
            100                 105                 110         


Leu Met Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg 
        115                 120                 125             


Lys Asp Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val 
    130                 135                 140                 


Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met 
145                 150                 155                 160 


Lys Glu Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp 
                165                 170                 175     


Tyr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            180                 185                 190         


Gly Gly Gly Gly Ser Met Ala Glu Val Gln Leu Val Gln Ser Gly Ala 
        195                 200                 205             


Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser 
    210                 215                 220                 


Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro 
225                 230                 235                 240 


Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly 
                245                 250                 255     


Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp 
            260                 265                 270         


Thr Ser Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp 
        275                 280                 285             


Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Gly Ser Ser Trp Tyr 
    290                 295                 300                 


Val Ala Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
305                 310                 315                 320 


Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala 
                325                 330                 335     


Ser Asp Ile Gln Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu 
            340                 345                 350         


Gly Glu Arg Ala Thr Ile Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr 
        355                 360                 365             


Lys Tyr Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly 
    370                 375                 380                 


Gln Pro Pro Lys Leu Ile Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly 
385                 390                 395                 400 


Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 
                405                 410                 415     


Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Val Tyr Tyr Cys Gln 
            420                 425                 430         


Gln Tyr Tyr Thr Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu 
        435                 440                 445             


Ile Lys Arg Ala Ala Ala Ser Ala 
    450                 455     


<210>  30
<211>  484
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of P2-E2-VHL, an exemplary chimaeric protein 
       of the first aspect of the invention

<400>  30

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 
            20                  25                  30          


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


Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Asp Tyr Gly Asp Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Val Met Thr Gln 
    130                 135                 140                 


Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 
145                 150                 155                 160 


Cys Arg Ala Ser Gln Thr Val Ser Thr Tyr Leu Ala Trp Tyr Gln Gln 
                165                 170                 175     


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Leu 
            180                 185                 190         


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
        195                 200                 205             


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Ala Ala Val Tyr 
    210                 215                 220                 


Tyr Cys Gln Gln Tyr Gly Ser Ser Val Ile Thr Phe Gly Gln Gly Thr 
225                 230                 235                 240 


Lys Leu Glu Ile Lys Arg Ala Ala Ala Ser Ala Gly Gly Gly Gly Ser 
                245                 250                 255     


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met 
            260                 265                 270         


Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu Glu 
        275                 280                 285             


Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu Ser 
    290                 295                 300                 


Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu Gly 
305                 310                 315                 320 


Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg Ser 
                325                 330                 335     


Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser Pro 
            340                 345                 350         


Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln Pro 
        355                 360                 365             


Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr Arg 
    370                 375                 380                 


Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu Leu 
385                 390                 395                 400 


Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly Gln 
                405                 410                 415     


Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu Arg 
            420                 425                 430         


Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg Arg 
        435                 440                 445             


Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro Asn 
    450                 455                 460                 


Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His Gln 
465                 470                 475                 480 


Arg Met Gly Asp 
                


<210>  31
<211>  492
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of P2-F3-VHL, an exemplary chimaeric protein 
       of the first aspect of the invention

<400>  31

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


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


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


Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln 
    50                  55                  60                  


Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr 
65                  70                  75                  80  


Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Gly Ser Ser Trp Tyr Val Ala Phe Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Gln Met 
    130                 135                 140                 


Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr 
145                 150                 155                 160 


Ile Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Lys Tyr Asn Asn Lys 
                165                 170                 175     


Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu 
            180                 185                 190         


Ile Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe 
        195                 200                 205             


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
    210                 215                 220                 


Gln Pro Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Thr Thr 
225                 230                 235                 240 


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


Ala Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
            260                 265                 270         


Gly Ser Gly Gly Gly Gly Ser Met Pro Arg Arg Ala Glu Asn Trp Asp 
        275                 280                 285             


Glu Ala Glu Val Gly Ala Glu Glu Ala Gly Val Glu Glu Tyr Gly Pro 
    290                 295                 300                 


Glu Glu Asp Gly Gly Glu Glu Ser Gly Ala Glu Glu Ser Gly Pro Glu 
305                 310                 315                 320 


Glu Ser Gly Pro Glu Glu Leu Gly Ala Glu Glu Glu Met Glu Ala Gly 
                325                 330                 335     


Arg Pro Arg Pro Val Leu Arg Ser Val Asn Ser Arg Glu Pro Ser Gln 
            340                 345                 350         


Val Ile Phe Cys Asn Arg Ser Pro Arg Val Val Leu Pro Val Trp Leu 
        355                 360                 365             


Asn Phe Asp Gly Glu Pro Gln Pro Tyr Pro Thr Leu Pro Pro Gly Thr 
    370                 375                 380                 


Gly Arg Arg Ile His Ser Tyr Arg Gly His Leu Trp Leu Phe Arg Asp 
385                 390                 395                 400 


Ala Gly Thr His Asp Gly Leu Leu Val Asn Gln Thr Glu Leu Phe Val 
                405                 410                 415     


Pro Ser Leu Asn Val Asp Gly Gln Pro Ile Phe Ala Asn Ile Thr Leu 
            420                 425                 430         


Pro Val Tyr Thr Leu Lys Glu Arg Cys Leu Gln Val Val Arg Ser Leu 
        435                 440                 445             


Val Lys Pro Glu Asn Tyr Arg Arg Leu Asp Ile Val Arg Ser Leu Tyr 
    450                 455                 460                 


Glu Asp Leu Glu Asp His Pro Asn Val Gln Lys Asp Leu Glu Arg Leu 
465                 470                 475                 480 


Thr Gln Glu Arg Ile Ala His Gln Arg Met Gly Asp 
                485                 490         


<210>  32
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of P2-E2-UBOX, an exemplary chimaeric protein
       of the first aspect of the invention

<400>  32

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 
            20                  25                  30          


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


Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Asp Tyr Gly Asp Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Val Met Thr Gln 
    130                 135                 140                 


Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 
145                 150                 155                 160 


Cys Arg Ala Ser Gln Thr Val Ser Thr Tyr Leu Ala Trp Tyr Gln Gln 
                165                 170                 175     


Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Leu 
            180                 185                 190         


Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
        195                 200                 205             


Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Ala Ala Val Tyr 
    210                 215                 220                 


Tyr Cys Gln Gln Tyr Gly Ser Ser Val Ile Thr Phe Gly Gln Gly Thr 
225                 230                 235                 240 


Lys Leu Glu Ile Lys Arg Ala Ala Ala Ser Ala Gly Gly Gly Gly Ser 
                245                 250                 255     


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg 
            260                 265                 270         


Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala Lys Lys 
        275                 280                 285             


Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu Ser Glu 
    290                 295                 300                 


Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu Arg Glu 
305                 310                 315                 320 


Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp Ser His 
                325                 330                 335     


Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys Tyr Met 
            340                 345                 350         


Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg Lys Lys 
        355                 360                 365             


Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu Leu Met 
    370                 375                 380                 


Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg Lys Asp 
385                 390                 395                 400 


Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val Thr Arg 
                405                 410                 415     


Ser Pro Leu Thr Gln Glu Gln Leu Ile Pro Asn Leu Ala Met Lys Glu 
            420                 425                 430         


Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp Tyr 
        435                 440                 445         


<210>  33
<211>  455
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of P2-F3-UBOX, an exemplary chimaeric protein
       of the first aspect of the invention

<400>  33

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


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


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


Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln 
    50                  55                  60                  


Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr 
65                  70                  75                  80  


Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Asp Arg Gly Ser Ser Trp Tyr Val Ala Phe Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Leu Glu Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Asp Ile Gln Met 
    130                 135                 140                 


Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr 
145                 150                 155                 160 


Ile Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Lys Tyr Asn Asn Lys 
                165                 170                 175     


Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu 
            180                 185                 190         


Ile Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe 
        195                 200                 205             


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
    210                 215                 220                 


Gln Pro Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Thr Thr 
225                 230                 235                 240 


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


Ala Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
            260                 265                 270         


Gly Ser Gly Gly Gly Gly Ser Arg Leu Asn Phe Gly Asp Asp Ile Pro 
        275                 280                 285             


Ser Ala Leu Arg Ile Ala Lys Lys Lys Arg Trp Asn Ser Ile Glu Glu 
    290                 295                 300                 


Arg Arg Ile His Gln Glu Ser Glu Leu His Ser Tyr Leu Ser Arg Leu 
305                 310                 315                 320 


Ile Ala Ala Glu Arg Glu Arg Glu Leu Glu Glu Cys Gln Arg Asn His 
                325                 330                 335     


Glu Gly Asp Glu Asp Asp Ser His Val Arg Ala Gln Gln Ala Cys Ile 
            340                 345                 350         


Glu Ala Lys His Asp Lys Tyr Met Ala Asp Met Asp Glu Leu Phe Ser 
        355                 360                 365             


Gln Val Asp Glu Lys Arg Lys Lys Arg Asp Ile Pro Asp Tyr Leu Cys 
    370                 375                 380                 


Gly Lys Ile Ser Phe Glu Leu Met Arg Glu Pro Cys Ile Thr Pro Ser 
385                 390                 395                 400 


Gly Ile Thr Tyr Asp Arg Lys Asp Ile Glu Glu His Leu Gln Arg Val 
                405                 410                 415     


Gly His Phe Asp Pro Val Thr Arg Ser Pro Leu Thr Gln Glu Gln Leu 
            420                 425                 430         


Ile Pro Asn Leu Ala Met Lys Glu Val Ile Asp Ala Phe Ile Ser Glu 
        435                 440                 445             


Asn Gly Trp Val Glu Asp Tyr 
    450                 455 


<210>  34
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of iDAb RAS-UBOX, an exemplary chimaeric 
       protein of the first aspect of the invention

<400>  34

Met Leu Cys Cys Met Arg Arg Thr Lys Gln Val Glu Lys Asn Asp Glu 
1               5                   10                  15      


Asp Gln Lys Ile Val Asp Met Asp Tyr Lys Asp Asp Asp Asp Arg Pro 
            20                  25                  30          


Met Ala Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro 
        35                  40                  45              


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser 
    50                  55                  60                  


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


Trp Val Ser Tyr Ile Ser Arg Thr Ser Lys Thr Ile Tyr Tyr Ala Asp 
                85                  90                  95      


Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 
            100                 105                 110         


Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 
        115                 120                 125             


Tyr Cys Ala Arg Gly Arg Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
    130                 135                 140                 


Val Thr Val Ser Ser Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Arg 
145                 150                 155                 160 


Leu Asn Phe Gly Asp Asp Ile Pro Ser Ala Leu Arg Ile Ala Lys Lys 
                165                 170                 175     


Lys Arg Trp Asn Ser Ile Glu Glu Arg Arg Ile His Gln Glu Ser Glu 
            180                 185                 190         


Leu His Ser Tyr Leu Ser Arg Leu Ile Ala Ala Glu Arg Glu Arg Glu 
        195                 200                 205             


Leu Glu Glu Cys Gln Arg Asn His Glu Gly Asp Glu Asp Asp Ser His 
    210                 215                 220                 


Val Arg Ala Gln Gln Ala Cys Ile Glu Ala Lys His Asp Lys Tyr Met 
225                 230                 235                 240 


Ala Asp Met Asp Glu Leu Phe Ser Gln Val Asp Glu Lys Arg Lys Lys 
                245                 250                 255     


Arg Asp Ile Pro Asp Tyr Leu Cys Gly Lys Ile Ser Phe Glu Leu Met 
            260                 265                 270         


Arg Glu Pro Cys Ile Thr Pro Ser Gly Ile Thr Tyr Asp Arg Lys Asp 
        275                 280                 285             


Ile Glu Glu His Leu Gln Arg Val Gly His Phe Asp Pro Val Thr Arg 
    290                 295                 300                 


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


Val Ile Asp Ala Phe Ile Ser Glu Asn Gly Trp Val Glu Asp Tyr 
                325                 330                 335 


<210>  35
<211>  371
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of VHL-iDAb RAS, an exemplary chimaeric 
       protein of the first aspect of the invention

<400>  35

Met Pro Arg Arg Ala Glu Asn Trp Asp Glu Ala Glu Val Gly Ala Glu 
1               5                   10                  15      


Glu Ala Gly Val Glu Glu Tyr Gly Pro Glu Glu Asp Gly Gly Glu Glu 
            20                  25                  30          


Ser Gly Ala Glu Glu Ser Gly Pro Glu Glu Ser Gly Pro Glu Glu Leu 
        35                  40                  45              


Gly Ala Glu Glu Glu Met Glu Ala Gly Arg Pro Arg Pro Val Leu Arg 
    50                  55                  60                  


Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg Ser 
65                  70                  75                  80  


Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro Gln 
                85                  90                  95      


Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser Tyr 
            100                 105                 110         


Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly Leu 
        115                 120                 125             


Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp Gly 
    130                 135                 140                 


Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys Glu 
145                 150                 155                 160 


Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr Arg 
                165                 170                 175     


Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His Pro 
            180                 185                 190         


Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala His 
        195                 200                 205             


Gln Arg Met Gly Asp Leu Glu Gly Gly Gly Gly Ser Ala Ala Ala Met 
    210                 215                 220                 


Asp Tyr Lys Asp Asp Asp Asp Lys Thr Ser Met Ala Glu Val Gln Leu 
225                 230                 235                 240 


Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 
                245                 250                 255     


Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Phe Ser Met Asn Trp 
            260                 265                 270         


Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Tyr Ile Ser 
        275                 280                 285             


Arg Thr Ser Lys Thr Ile Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
    290                 295                 300                 


Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn 
305                 310                 315                 320 


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Arg 
                325                 330                 335     


Phe Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Lys 
            340                 345                 350         


Leu Asn Pro Pro Asp Glu Ser Gly Pro Gly Cys Met Ser Cys Lys Cys 
        355                 360                 365             


Val Leu Ser 
    370     


<210>  36
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of primer DUSP6For

<400>  36
ctcggatcac tggagccaaa ac                                                22


<210>  37
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of primer DUSP6Rev

<400>  37
gtcacagtga ctgagcggct aa                                                22


<210>  38
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of primer GAPDHFor

<400>  38
gtctcctctg acttcaacag cg                                                22


<210>  39
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  DNA sequence of primer GAPDHRev

<400>  39
accaccctgt tgctgtagcc aa                                                22


<210>  40
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of optional sequence within certain exemplary
       proteins of the invention

<400>  40

Val Asp Gly Gly Ser 
1               5   


<210>  41
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of optional FLAG tag sequence in exemplary 
       proteins of the invention

<400>  41

Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5               


