                         SEQUENCE LISTING

<110>  Deutsche Rheuma-Forschungszentrum Berlin
       Engelhardt Institute of Molecular Biology, Russian Academy 
       of Sciences
 
<120>  Bi-specific affinity reagents for cell-lineage-specific TNF-alpha
        neutralisation

<130>  XII 732/13

<160>  22    

<170>  PatentIn version 3.3

<210>  1
<211>  135
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  1

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


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


Ser Asp His Ser Gly Tyr Thr Tyr Thr Ile Gly Trp Phe Arg Gln Ala 
        35                  40                  45              


Pro Gly Lys Glu Arg Glu Phe Val Ala Arg Ile Tyr Trp Ser Ser Gly 
    50                  55                  60                  


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


Asp Ile Ala Lys Asn Thr Val Asp Leu Thr Met Asn Asn Leu Glu Pro 
                85                  90                  95      


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Arg Asp Gly Ile Pro Thr 
            100                 105                 110         


Ser Arg Ser Val Glu Ser Tyr Asn Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             


Thr Val Ser Ser Ala Gly Ala 
    130                 135 


<210>  2
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  2

Gly Tyr Thr Phe Thr Asn His Met Asn 
1               5                   


<210>  3
<211>  17
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  3

Arg Ile Asn Pro Gly Thr Gly Gly Thr Ser Tyr Asn Val Asn Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  4
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  4

Gly Asp Ser Tyr Trp Tyr Phe Asp Phe 
1               5                   


<210>  5
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  5

Lys Ala Ser Lys Ser Ile Ser Lys Tyr Leu Ala 
1               5                   10      


<210>  6
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  6

Glu Gly Ser Thr Leu Gln Ser 
1               5           


<210>  7
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  7

Gln Gln His Asn Glu Tyr Pro Leu Thr 
1               5                   


<210>  8
<211>  119
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  8

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


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


His Met Asn Trp Val Lys Gln Thr Thr Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Arg Ile Asn Pro Gly Thr Gly Gly Thr Ser Tyr Asn Val Asn Phe 
    50                  55                  60                  


Lys Gly Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Phe 
65                  70                  75                  80  


Met Gln Leu Ser Ser Leu Thr Pro Glu Asp Ser Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Asp Ser Tyr Trp Tyr Phe Asp Phe Trp Gly Pro Gly Thr 
            100                 105                 110         


Met Val Thr Val Ser Gly Ser 
        115                 


<210>  9
<211>  138
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  9

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


Glu Ser Val Ser Ile Asn Cys Lys Ala Ser Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Asn Lys Leu Leu Ile 
        35                  40                  45              


Tyr Glu Gly Ser Thr Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Ser Leu Glu Pro 
65                  70                  75                  80  


Glu Asp Phe Gly Leu Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Leu 
                85                  90                  95      


Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala 
            100                 105                 110         


Pro Thr Val Ala Ala Ala Pro Arg Gly Gly Pro Glu Gln Lys Leu Ile 
        115                 120                 125             


Ser Glu Glu Asp Leu Asn Ser Ala Val Asp 
    130                 135             


<210>  10
<211>  415
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody fragment

<400>  10

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


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


Ser Asp His Ser Gly Tyr Thr Tyr Thr Ile Gly Trp Phe Arg Gln Ala 
        35                  40                  45              


Pro Gly Lys Glu Arg Glu Phe Val Ala Arg Ile Tyr Trp Ser Ser Gly 
    50                  55                  60                  


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


Asp Ile Ala Lys Asn Thr Val Asp Leu Thr Met Asn Asn Leu Glu Pro 
                85                  90                  95      


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Arg Asp Gly Ile Pro Thr 
            100                 105                 110         


Ser Arg Ser Val Glu Ser Tyr Asn Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             


Thr Val Ser Ser Ala Gly Ala Gly Ser Gly Gly Gly Gly Ser Gly Met 
    130                 135                 140                 


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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn His 
                165                 170                 175     


Met Asn Trp Val Lys Gln Thr Thr Gly Gln Gly Leu Glu Trp Ile Gly 
            180                 185                 190         


Arg Ile Asn Pro Gly Thr Gly Gly Thr Ser Tyr Asn Val Asn Phe Lys 
        195                 200                 205             


Gly Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Phe Met 
    210                 215                 220                 


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


Arg Gly Asp Ser Tyr Trp Tyr Phe Asp Phe Trp Gly Pro Gly Thr Met 
                245                 250                 255     


Val Thr Val Ser Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            260                 265                 270         


Gly Gly Gly Gly Ser Asp Val Gln Met Thr Gln Ser Pro Tyr Asn Leu 
        275                 280                 285             


Val Ala Ser Pro Gly Glu Ser Val Ser Ile Asn Cys Lys Ala Ser Lys 
    290                 295                 300                 


Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala 
305                 310                 315                 320 


Asn Lys Leu Leu Ile Tyr Glu Gly Ser Thr Leu Gln Ser Gly Ile Pro 
                325                 330                 335     


Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
            340                 345                 350         


Arg Ser Leu Glu Pro Glu Asp Phe Gly Leu Tyr Tyr Cys Gln Gln His 
        355                 360                 365             


Asn Glu Tyr Pro Leu Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
    370                 375                 380                 


Arg Ala Asp Ala Ala Pro Thr Val Ala Ala Ala Pro Arg Gly Gly Pro 
385                 390                 395                 400 


Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Ser Ala Val Asp 
                405                 410                 415 


<210>  11
<211>  405
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  11
atgggttccc aagttcagct tcaagaatct ggtggaggac ttgttcaacc tggtggatct     60

cttaggcttt cttgcgctgc ttctggaagg actttctctg atcactctgg atacacttac    120

actattggat ggttcagaca ggctccagga aaagagagag agttcgttgc taggatctac    180

tggtcatctg gaaacactta ctacgctgat tctgtgaagg gaagattcgc tatttctagg    240

gatattgcta agaacactgt ggatcttact atgaacaacc ttgagccaga ggatactgct    300

gtttactatt gcgctgctag ggatggaatt ccaacttcta gatctgtgga gtcttacaac    360

tactggggac agggaactca agtgactgtt tcttctgccg gcgcg                    405


<210>  12
<211>  30
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  12
ggttatacct ttacccgcaa tcatatgaat                                      30


<210>  13
<211>  51
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  13
cgtattaatc cgggtacagg tggcaccagc tataatgtga attttaaagg c              51


<210>  14
<211>  27
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  14
ggcgatagct attggtattt tgatttt                                         27


<210>  15
<211>  33
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  15
aaagccagca aaagcattag caaatatctg gca                                  33


<210>  16
<211>  21
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  16
gaaggtagca ccctgcagag c                                               21


<210>  17
<211>  27
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  17
cagcagcata atgaatatcc gctgacc                                         27


<210>  18
<211>  360
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  18
atgcaggttc agctgcagca gagcggtgca gaactggtta aaccgggtac aagcgttaaa     60

ctgagctgta aagcaagcgg ttataccttt acccgcaatc atatgaattg ggtgaaacag    120

accaccggtc agggtctgga atggattggt cgtattaatc cgggtacagg tggcaccagc    180

tataatgtga attttaaagg caaagcaacc ctgaccgttg atgaaagcag cagcaccgca    240

tttatgcagc tgagcagcct gacaccggaa gatagcgcag tgtactactg tgcacgtggc    300

gatagctatt ggtattttga tttttggggt ccgggtacaa tggttaccgt tagcggtagc    360


<210>  19
<211>  415
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  19
gatgttcaga tgacccagag cccgtataat ctggttgcat ctccgggtga aagcgttagc     60

attaattgca aagccagcaa aagcattagc aaatatctgg catggtatca gcagaaaccg    120

ggtaaagcaa ataaactgct gatttatgaa ggtagcaccc tgcagagcgg tattccgagc    180

cgttttagcg gttctggtag cggcaccgat tttaccctga ccattcgtag cctggaaccg    240

gaagattttg gtctgtatta ttgccagcag cataatgaat atccgctgac ctttggtagc    300

ggtacaaaac tggaaattaa acgtgcagat gcagcaccga ccgttgcagc agctccgcgt    360

ggtggtccgg aacagaaact gattagcgaa gaagatctga atagcgcagt tgatc         415


<210>  20
<211>  1249
<212>  DNA
<213>  Artificial

<220>
<223>  Antibody fragment DNA

<400>  20
atgggttccc aagttcagct tcaagaatct ggtggaggac ttgttcaacc tggtggatct     60

cttaggcttt cttgcgctgc ttctggaagg actttctctg atcactctgg atacacttac    120

actattggat ggttcagaca ggctccagga aaagagagag agttcgttgc taggatctac    180

tggtcatctg gaaacactta ctacgctgat tctgtgaagg gaagattcgc tatttctagg    240

gatattgcta agaacactgt ggatcttact atgaacaacc ttgagccaga ggatactgct    300

gtttactatt gcgctgctag ggatggaatt ccaacttcta gatctgtgga gtcttacaac    360

tactggggac agggaactca agtgactgtt tcttctgccg gcgcgggatc cggtggtggt    420

ggtagcggta tgcaggttca gctgcagcag agcggtgcag aactggttaa accgggtaca    480

agcgttaaac tgagctgtaa agcaagcggt tataccttta cccgcaatca tatgaattgg    540

gtgaaacaga ccaccggtca gggtctggaa tggattggtc gtattaatcc gggtacaggt    600

ggcaccagct ataatgtgaa ttttaaaggc aaagcaaccc tgaccgttga tgaaagcagc    660

agcaccgcat ttatgcagct gagcagcctg acaccggaag atagcgcagt gtactactgt    720

gcacgtggcg atagctattg gtattttgat ttttggggtc cgggtacaat ggttaccgtt    780

agcggtagcg gtggtggcgg ttctggtggt ggtggctcag gtggcggtgg ttctgatgtt    840

cagatgaccc agagcccgta taatctggtt gcatctccgg gtgaaagcgt tagcattaat    900

tgcaaagcca gcaaaagcat tagcaaatat ctggcatggt atcagcagaa accgggtaaa    960

gcaaataaac tgctgattta tgaaggtagc accctgcaga gcggtattcc gagccgtttt   1020

agcggttctg gtagcggcac cgattttacc ctgaccattc gtagcctgga accggaagat   1080

tttggtctgt attattgcca gcagcataat gaatatccgc tgacctttgg tagcggtaca   1140

aaactggaaa ttaaacgtgc agatgcagca ccgaccgttg cagcagctcc gcgtggtggt   1200

ccggaacaga aactgattag cgaagaagat ctgaatagcg cagttgatc               1249


<210>  21
<211>  424
<212>  PRT
<213>  artificial

<220>
<223>  antibody construct

<400>  21

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


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


Ser Asp His Ser Gly Tyr Thr Tyr Thr Ile Gly Trp Phe Arg Gln Ala 
        35                  40                  45              


Pro Gly Lys Glu Arg Glu Phe Val Ala Arg Ile Tyr Trp Ser Ser Gly 
    50                  55                  60                  


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


Asp Ile Ala Lys Asn Thr Val Asp Leu Thr Met Asn Asn Leu Glu Pro 
                85                  90                  95      


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Arg Asp Gly Ile Pro Thr 
            100                 105                 110         


Ser Arg Ser Val Glu Ser Tyr Asn Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             


Thr Val Ser Ser Ala Gly Ala Gly Ser Gly Gly Gly Gly Ser Gly Met 
    130                 135                 140                 


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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Arg Asn 
                165                 170                 175     


His Met Asn Trp Val Lys Gln Thr Thr Gly Gln Gly Leu Glu Trp Ile 
            180                 185                 190         


Gly Arg Ile Asn Pro Gly Thr Gly Gly Thr Ser Tyr Asn Val Asn Phe 
        195                 200                 205             


Lys Gly Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Phe 
    210                 215                 220                 


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


Ala Arg Gly Asp Ser Tyr Trp Tyr Phe Asp Phe Trp Gly Pro Gly Thr 
                245                 250                 255     


Met Val Thr Val Ser Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            260                 265                 270         


Ser Gly Gly Gly Gly Ser Asp Val Gln Met Thr Gln Ser Pro Tyr Asn 
        275                 280                 285             


Leu Val Ala Ser Pro Gly Glu Ser Val Ser Ile Asn Cys Lys Ala Ser 
    290                 295                 300                 


Lys Ser Ile Ser Lys Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
305                 310                 315                 320 


Ala Asn Lys Leu Leu Ile Tyr Glu Gly Ser Thr Leu Gln Ser Gly Ile 
                325                 330                 335     


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
            340                 345                 350         


Ile Arg Ser Leu Glu Pro Glu Asp Phe Gly Leu Tyr Tyr Cys Gln Gln 
        355                 360                 365             


His Asn Glu Tyr Pro Leu Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile 
    370                 375                 380                 


Lys Arg Ala Asp Ala Ala Pro Thr Val Ala Ala Ala Pro Arg Gly Gly 
385                 390                 395                 400 


Pro Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Ser Ala Val Asp 
                405                 410                 415     


Leu Glu His His His His His His 
            420                 


<210>  22
<211>  424
<212>  PRT
<213>  artificial

<220>
<223>  antibody construct

<400>  22

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


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


Ser Asp His Ser Gly Tyr Thr Tyr Thr Ile Gly Trp Phe Arg Gln Ala 
        35                  40                  45              


Pro Gly Lys Glu Arg Glu Phe Val Ala Arg Ile Tyr Trp Ser Ser Gly 
    50                  55                  60                  


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


Asp Ile Ala Lys Asn Thr Val Asp Leu Thr Met Asn Asn Leu Glu Pro 
                85                  90                  95      


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Arg Asp Gly Ile Pro Thr 
            100                 105                 110         


Ser Arg Ser Val Glu Ser Tyr Asn Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             


Thr Val Ser Ser Ala Gly Ala Gly Ser Gly Gly Gly Gly Ser Gly Met 
    130                 135                 140                 


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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Gly Gly Gly Ser Gly Gly 
                165                 170                 175     


Gly Gly Ser Trp Val Lys Gln Thr Thr Gly Gln Gly Leu Glu Trp Ile 
            180                 185                 190         


Gly Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        195                 200                 205             


Gly Ser Lys Ala Thr Leu Thr Val Asp Glu Ser Ser Ser Thr Ala Phe 
    210                 215                 220                 


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


Ala Arg Gly Gly Gly Ser Gly Gly Gly Gly Ser Trp Gly Pro Gly Thr 
                245                 250                 255     


Met Val Thr Val Ser Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            260                 265                 270         


Ser Gly Gly Gly Gly Ser Asp Val Gln Met Thr Gln Ser Pro Tyr Asn 
        275                 280                 285             


Leu Val Ala Ser Pro Gly Glu Ser Val Ser Ile Asn Cys Gly Gly Gly 
    290                 295                 300                 


Gly Ser Gly Gly Gly Gly Ser Gly Trp Tyr Gln Gln Lys Pro Gly Lys 
305                 310                 315                 320 


Ala Asn Lys Leu Leu Ile Tyr Gly Ser Gly Gly Gly Ser Gly Gly Ile 
                325                 330                 335     


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
            340                 345                 350         


Ile Arg Ser Leu Glu Pro Glu Asp Phe Gly Leu Tyr Tyr Cys Gly Gly 
        355                 360                 365             


Gly Ser Gly Gly Gly Gly Ser Phe Gly Ser Gly Thr Lys Leu Glu Ile 
    370                 375                 380                 


Lys Arg Ala Asp Ala Ala Pro Thr Val Ala Ala Ala Pro Arg Gly Gly 
385                 390                 395                 400 


Pro Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Ser Ala Val Asp 
                405                 410                 415     


Leu Glu His His His His His His 
            420                 


