                         SEQUENCE LISTING

<110>  PIERRE FABRE MEDICAMENT
 
<120>  NOVEL ANTI ADAM17 ANTIBODY AND ITS USE FOR THE TREATMENT OF 
       CANCER

<130>  366742D33276

<150>  EP13306860.1
<151>  2013-12-24

<160>  38    

<170>  PatentIn version 3.5

<210>  1
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (X1)


<220>
<221>  VARIANT
<222>  (5)..(5)
<223>  X is N, D, Q, S, E, R, K, H, W, Y or T

<400>  1

Gly Phe Ser Leu Xaa Thr Ser Gly Met Gly 
1               5                   10  


<210>  2
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H2

<400>  2

Ile Tyr Trp Asp Asp Asp Lys 
1               5           


<210>  3
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H3

<400>  3

Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
1               5                   10                  15  


<210>  4
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L1

<400>  4

Gln Asp Ile Ser Ser Tyr 
1               5       


<210>  5
<211>  3
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L2

<400>  5

Tyr Thr Ser 
1           


<210>  6
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L3

<400>  6

Gln Gln Gly Lys Thr Leu Pro Leu Thr 
1               5                   


<210>  7
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (N)

<400>  7

Gly Phe Ser Leu Asn Thr Ser Gly Met Gly 
1               5                   10  


<210>  8
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (D)

<400>  8

Gly Phe Ser Leu Asp Thr Ser Gly Met Gly 
1               5                   10  


<210>  9
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (X1)


<220>
<221>  VARIANT
<222>  (30)..(30)
<223>  X is N, D, Q, S, E, R, K, H, W, Y or T

<400>  9

Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Xaa Thr Ser 
            20                  25                  30          


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


Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val 
65                  70                  75                  80  


Phe Leu Lys Ile Thr Ser Leu Asp Thr Ala Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Ser Val Thr Val Thr Ser 
        115                 120             


<210>  10
<211>  107
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody light chain variable domain

<400>  10

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


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile 
        35                  40                  45              


Phe Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Ser Lys Tyr Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Ala Tyr Phe Cys Gln Gln Gly Lys Thr Leu Pro Leu 
                85                  90                  95      


Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105         


<210>  11
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (N)

<400>  11

Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Asn Thr Ser 
            20                  25                  30          


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


Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val 
65                  70                  75                  80  


Phe Leu Lys Ile Thr Ser Leu Asp Thr Ala Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Ser Val Thr Val Thr Ser 
        115                 120             


<210>  12
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (D)

<400>  12

Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Asp Thr Ser 
            20                  25                  30          


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


Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val 
65                  70                  75                  80  


Phe Leu Lys Ile Thr Ser Leu Asp Thr Ala Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Ser Val Thr Val Thr Ser 
        115                 120             


<210>  13
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (X2)


<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  nnn is AAC, AAT, GAC, GAT, CAG, CAA, TCG, TCT, TCA, TCC, AGT, 
       AGC, GAA, GAG, CGA, CGT, CGC, CGG, AGA, AGG, AAA, AAG, CAT, CAC, 
       TGG, TAT, TAC, ACT, ACC, ACG or ACA

<400>  13
gggttttcac tgnnnacttc tggtatgggt                                        30


<210>  14
<211>  21
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H2

<400>  14
atttactggg atgacgacaa g                                                 21


<210>  15
<211>  45
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H3

<400>  15
gctcgaagat ctcactttgg taactattac tatgctatgg actac                       45


<210>  16
<211>  18
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L1

<400>  16
caggacatta gtagttat                                                     18


<210>  17
<211>  9
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L2

<400>  17
tacacatca                                                                9


<210>  18
<211>  27
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-L3

<400>  18
caacagggta aaacacttcc gctcacg                                           27


<210>  19
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (aac)

<400>  19
gggttttcac tgaacacttc tggtatgggt                                        30


<210>  20
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (aat)

<400>  20
gggttttcac tgaatacttc tggtatgggt                                        30


<210>  21
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (gac)

<400>  21
gggttttcac tggacacttc tggtatgggt                                        30


<210>  22
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody CDR-H1 (gat)

<400>  22
gggttttcac tggatacttc tggtatgggt                                        30


<210>  23
<211>  369
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (X2)


<220>
<221>  misc_feature
<222>  (88)..(90)
<223>  nnn is AAC, AAT, GAC, GAT, CAG, CAA, TCG, TCT, TCA, TCC, AGT, 
       AGC, GAA, GAG, CGA, CGT, CGC, CGG, AGA, AGG, AAA, AAG, CAT, CAC, 
       TGG, TAT, TAC, ACT, ACC, ACG or ACA

<400>  23
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg       60

acttgttctt tctctgggtt ttcactgnnn acttctggta tgggtgtgag ctggattcgt      120

cagccttcag gaaagggtct ggagtggctg gcacacattt actgggatga cgacaagcgc      180

tataatccat ccctgaagag ccggctcaca atctccaagg atacctccag caaccaggtt      240

ttcctcaaga tcaccagttt ggacactgca gatactgcca catactactg tgctcgaaga      300

tctcactttg gtaactatta ctatgctatg gactactggg gtcaaggaac ctcagtcacc      360

gtcacctca                                                              369


<210>  24
<211>  369
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (aac)

<400>  24
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg       60

acttgttctt tctctgggtt ttcactgaac acttctggta tgggtgtgag ctggattcgt      120

cagccttcag gaaagggtct ggagtggctg gcacacattt actgggatga cgacaagcgc      180

tataatccat ccctgaagag ccggctcaca atctccaagg atacctccag caaccaggtt      240

ttcctcaaga tcaccagttt ggacactgca gatactgcca catactactg tgctcgaaga      300

tctcactttg gtaactatta ctatgctatg gactactggg gtcaaggaac ctcagtcacc      360

gtcacctca                                                              369


<210>  25
<211>  369
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (gat)

<400>  25
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg       60

acttgttctt tctctgggtt ttcactggat acttctggta tgggtgtgag ctggattcgt      120

cagccttcag gaaagggtct ggagtggctg gcacacattt actgggatga cgacaagcgc      180

tataatccat ccctgaagag ccggctcaca atctccaagg atacctccag caaccaggtt      240

ttcctcaaga tcaccagttt ggacactgca gatactgcca catactactg tgctcgaaga      300

tctcactttg gtaactatta ctatgctatg gactactggg gtcaaggaac ctcagtcacc      360

gtcacctca                                                              369


<210>  26
<211>  321
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody light chain variable domain

<400>  26
gatgtccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc       60

atcagttgca gggcaagtca ggacattagt agttatttaa attggtatca gcagaaacca      120

gatggaactt ttaaactcct gatcttctac acatcaagat tacagtcagg agtcccatca      180

aaatacagtg gcagtgggtc tggaacagat tattctctca ccattagtaa cctggagcaa      240

gaagatattg ccgcttactt ttgccaacag ggtaaaacac ttccgctcac gttcggggct      300

gggaccaagc tggaactgaa a                                                321


<210>  27
<211>  369
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (aat)

<400>  27
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg       60

acttgttctt tctctgggtt ttcactgaat acttctggta tgggtgtgag ctggattcgt      120

cagccttcag gaaagggtct ggagtggctg gcacacattt actgggatga cgacaagcgc      180

tataatccat ccctgaagag ccggctcaca atctccaagg atacctccag caaccaggtt      240

ttcctcaaga tcaccagttt ggacactgca gatactgcca catactactg tgctcgaaga      300

tctcactttg gtaactatta ctatgctatg gactactggg gtcaaggaac ctcagtcacc      360

gtcacctca                                                              369


<210>  28
<211>  369
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain variable domain (gac)

<400>  28
caggttactc tgaaagagtc tggccctggg atattgcagc cctcccagac cctcagtctg       60

acttgttctt tctctgggtt ttcactggac acttctggta tgggtgtgag ctggattcgt      120

cagccttcag gaaagggtct ggagtggctg gcacacattt actgggatga cgacaagcgc      180

tataatccat ccctgaagag ccggctcaca atctccaagg atacctccag caaccaggtt      240

ttcctcaaga tcaccagttt ggacactgca gatactgcca catactactg tgctcgaaga      300

tctcactttg gtaactatta ctatgctatg gactactggg gtcaaggaac ctcagtcacc      360

gtcacctca                                                              369


<210>  29
<211>  824
<212>  PRT
<213>  artificial

<220>
<223>  ADAM17

<400>  29

Met Arg Gln Ser Leu Leu Phe Leu Thr Ser Val Val Pro Phe Val Leu 
1               5                   10                  15      


Ala Pro Arg Pro Pro Asp Asp Pro Gly Phe Gly Pro His Gln Arg Leu 
            20                  25                  30          


Glu Lys Leu Asp Ser Leu Leu Ser Asp Tyr Asp Ile Leu Ser Leu Ser 
        35                  40                  45              


Asn Ile Gln Gln His Ser Val Arg Lys Arg Asp Leu Gln Thr Ser Thr 
    50                  55                  60                  


His Val Glu Thr Leu Leu Thr Phe Ser Ala Leu Lys Arg His Phe Lys 
65                  70                  75                  80  


Leu Tyr Leu Thr Ser Ser Thr Glu Arg Phe Ser Gln Asn Phe Lys Val 
                85                  90                  95      


Val Val Val Asp Gly Lys Asn Glu Ser Glu Tyr Thr Val Lys Trp Gln 
            100                 105                 110         


Asp Phe Phe Thr Gly His Val Val Gly Glu Pro Asp Ser Arg Val Leu 
        115                 120                 125             


Ala His Ile Arg Asp Asp Asp Val Ile Ile Arg Ile Asn Thr Asp Gly 
    130                 135                 140                 


Ala Glu Tyr Asn Ile Glu Pro Leu Trp Arg Phe Val Asn Asp Thr Lys 
145                 150                 155                 160 


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


Arg Leu Gln Ser Pro Lys Val Cys Gly Tyr Leu Lys Val Asp Asn Glu 
            180                 185                 190         


Glu Leu Leu Pro Lys Gly Leu Val Asp Arg Glu Pro Pro Glu Glu Leu 
        195                 200                 205             


Val His Arg Val Lys Arg Arg Ala Asp Pro Asp Pro Met Lys Asn Thr 
    210                 215                 220                 


Cys Lys Leu Leu Val Val Ala Asp His Arg Phe Tyr Arg Tyr Met Gly 
225                 230                 235                 240 


Arg Gly Glu Glu Ser Thr Thr Thr Asn Tyr Leu Ile Glu Leu Ile Asp 
                245                 250                 255     


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


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


Gln Glu Val Lys Pro Gly Glu Lys His Tyr Asn Met Ala Lys Ser Tyr 
    290                 295                 300                 


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


Phe Ser Phe Asp Ile Ala Glu Glu Ala Ser Lys Val Cys Leu Ala His 
                325                 330                 335     


Leu Phe Thr Tyr Gln Asp Phe Asp Met Gly Thr Leu Gly Leu Ala Tyr 
            340                 345                 350         


Val Gly Ser Pro Arg Ala Asn Ser His Gly Gly Val Cys Pro Lys Ala 
        355                 360                 365             


Tyr Tyr Ser Pro Val Gly Lys Lys Asn Ile Tyr Leu Asn Ser Gly Leu 
    370                 375                 380                 


Thr Ser Thr Lys Asn Tyr Gly Lys Thr Ile Leu Thr Lys Glu Ala Asp 
385                 390                 395                 400 


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


Pro Asp Gly Leu Ala Glu Cys Ala Pro Asn Glu Asp Gln Gly Gly Lys 
            420                 425                 430         


Tyr Val Met Tyr Pro Ile Ala Val Ser Gly Asp His Glu Asn Asn Lys 
        435                 440                 445             


Met Phe Ser Asn Cys Ser Lys Gln Ser Ile Tyr Lys Thr Ile Glu Ser 
    450                 455                 460                 


Lys Ala Gln Glu Cys Phe Gln Glu Arg Ser Asn Lys Val Cys Gly Asn 
465                 470                 475                 480 


Ser Arg Val Asp Glu Gly Glu Glu Cys Asp Pro Gly Ile Met Tyr Leu 
                485                 490                 495     


Asn Asn Asp Thr Cys Cys Asn Ser Asp Cys Thr Leu Lys Glu Gly Val 
            500                 505                 510         


Gln Cys Ser Asp Arg Asn Ser Pro Cys Cys Lys Asn Cys Gln Phe Glu 
        515                 520                 525             


Thr Ala Gln Lys Lys Cys Gln Glu Ala Ile Asn Ala Thr Cys Lys Gly 
    530                 535                 540                 


Val Ser Tyr Cys Thr Gly Asn Ser Ser Glu Cys Pro Pro Pro Gly Asn 
545                 550                 555                 560 


Ala Glu Asp Asp Thr Val Cys Leu Asp Leu Gly Lys Cys Lys Asp Gly 
                565                 570                 575     


Lys Cys Ile Pro Phe Cys Glu Arg Glu Gln Gln Leu Glu Ser Cys Ala 
            580                 585                 590         


Cys Asn Glu Thr Asp Asn Ser Cys Lys Val Cys Cys Arg Asp Leu Ser 
        595                 600                 605             


Gly Arg Cys Val Pro Tyr Val Asp Ala Glu Gln Lys Asn Leu Phe Leu 
    610                 615                 620                 


Arg Lys Gly Lys Pro Cys Thr Val Gly Phe Cys Asp Met Asn Gly Lys 
625                 630                 635                 640 


Cys Glu Lys Arg Val Gln Asp Val Ile Glu Arg Phe Trp Asp Phe Ile 
                645                 650                 655     


Asp Gln Leu Ser Ile Asn Thr Phe Gly Lys Phe Leu Ala Asp Asn Ile 
            660                 665                 670         


Val Gly Ser Val Leu Val Phe Ser Leu Ile Phe Trp Ile Pro Phe Ser 
        675                 680                 685             


Ile Leu Val His Cys Val Asp Lys Lys Leu Asp Lys Gln Tyr Glu Ser 
    690                 695                 700                 


Leu Ser Leu Phe His Pro Ser Asn Val Glu Met Leu Ser Ser Met Asp 
705                 710                 715                 720 


Ser Ala Ser Val Arg Ile Ile Lys Pro Phe Pro Ala Pro Gln Thr Pro 
                725                 730                 735     


Gly Arg Leu Gln Pro Ala Pro Val Ile Pro Ser Ala Pro Ala Ala Pro 
            740                 745                 750         


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


Asp Ser His Met Asp Glu Asp Gly Phe Glu Lys Asp Pro Phe Pro Asn 
    770                 775                 780                 


Ser Ser Thr Ala Ala Lys Ser Phe Glu Asp Leu Thr Asp His Pro Val 
785                 790                 795                 800 


Thr Arg Ser Glu Lys Ala Ala Ser Phe Lys Leu Gln Arg Gln Asn Arg 
                805                 810                 815     


Val Asp Ser Lys Glu Thr Glu Cys 
            820                 


<210>  30
<211>  260
<212>  PRT
<213>  artificial

<220>
<223>  Metalloprotease domain of ADAM17

<400>  30

Arg Ala Asp Pro Asp Pro Met Lys Asn Thr Cys Lys Leu Leu Val Val 
1               5                   10                  15      


Ala Asp His Arg Phe Tyr Arg Tyr Met Gly Arg Gly Glu Glu Ser Thr 
            20                  25                  30          


Thr Thr Asn Tyr Leu Ile Glu Leu Ile Asp Arg Val Asp Asp Ile Tyr 
        35                  40                  45              


Arg Asn Thr Ser Trp Asp Asn Ala Gly Phe Lys Gly Tyr Gly Ile Gln 
    50                  55                  60                  


Ile Glu Gln Ile Arg Ile Leu Lys Ser Pro Gln Glu Val Lys Pro Gly 
65                  70                  75                  80  


Glu Lys His Tyr Asn Met Ala Lys Ser Tyr Pro Asn Glu Glu Lys Asp 
                85                  90                  95      


Ala Trp Asp Val Lys Met Leu Leu Glu Gln Phe Ser Phe Asp Ile Ala 
            100                 105                 110         


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


Phe Asp Met Gly Thr Leu Gly Leu Ala Tyr Val Gly Ser Pro Arg Ala 
    130                 135                 140                 


Asn Ser His Gly Gly Val Cys Pro Lys Ala Tyr Tyr Ser Pro Val Gly 
145                 150                 155                 160 


Lys Lys Asn Ile Tyr Leu Asn Ser Gly Leu Thr Ser Thr Lys Asn Tyr 
                165                 170                 175     


Gly Lys Thr Ile Leu Thr Lys Glu Ala Asp Leu Val Thr Thr His Glu 
            180                 185                 190         


Leu Gly His Asn Phe Gly Ala Glu His Asp Pro Asp Gly Leu Ala Glu 
        195                 200                 205             


Cys Ala Pro Asn Glu Asp Gln Gly Gly Lys Tyr Val Met Tyr Pro Ile 
    210                 215                 220                 


Ala Val Ser Gly Asp His Glu Asn Asn Lys Met Phe Ser Asn Cys Ser 
225                 230                 235                 240 


Lys Gln Ser Ile Tyr Lys Thr Ile Glu Ser Lys Ala Gln Glu Cys Phe 
                245                 250                 255     


Gln Glu Arg Ser 
            260 


<210>  31
<211>  89
<212>  PRT
<213>  artificial

<220>
<223>  Disintegrin domain of ADAM17

<400>  31

Asn Lys Val Cys Gly Asn Ser Arg Val Asp Glu Gly Glu Glu Cys Asp 
1               5                   10                  15      


Pro Gly Ile Met Tyr Leu Asn Asn Asp Thr Cys Cys Asn Ser Asp Cys 
            20                  25                  30          


Thr Leu Lys Glu Gly Val Gln Cys Ser Asp Arg Asn Ser Pro Cys Cys 
        35                  40                  45              


Lys Asn Cys Gln Phe Glu Thr Ala Gln Lys Lys Cys Gln Glu Ala Ile 
    50                  55                  60                  


Asn Ala Thr Cys Lys Gly Val Ser Tyr Cys Thr Gly Asn Ser Ser Glu 
65                  70                  75                  80  


Cys Pro Pro Pro Gly Asn Ala Glu Asp 
                85                  


<210>  32
<211>  108
<212>  PRT
<213>  artificial

<220>
<223>  Membrane proximal domain of ADAM17

<400>  32

Asp Thr Val Cys Leu Asp Leu Gly Lys Cys Lys Asp Gly Lys Cys Ile 
1               5                   10                  15      


Pro Phe Cys Glu Arg Glu Gln Gln Leu Glu Ser Cys Ala Cys Asn Glu 
            20                  25                  30          


Thr Asp Asn Ser Cys Lys Val Cys Cys Arg Asp Leu Ser Gly Arg Cys 
        35                  40                  45              


Val Pro Tyr Val Asp Ala Glu Gln Lys Asn Leu Phe Leu Arg Lys Gly 
    50                  55                  60                  


Lys Pro Cys Thr Val Gly Phe Cys Asp Met Asn Gly Lys Cys Glu Lys 
65                  70                  75                  80  


Arg Val Gln Asp Val Ile Glu Arg Phe Trp Asp Phe Ile Asp Gln Leu 
                85                  90                  95      


Ser Ile Asn Thr Phe Gly Lys Phe Leu Ala Asp Asn 
            100                 105             


<210>  33
<211>  453
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain Chimeric (c) IgG1

<400>  33

Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Asn Thr Ser 
            20                  25                  30          


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


Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val 
65                  70                  75                  80  


Phe Leu Lys Ile Thr Ser Leu Asp Thr Ala Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Ser Val Thr Val Thr Ser Ala Ser Thr Lys Gly 
        115                 120                 125             


Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 


Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 


Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     


Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         


Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             


Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 
    210                 215                 220                 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser Pro Gly Lys 
    450             


<210>  34
<211>  452
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain Chimeric (c) IgG1 AlaAla

<400>  34

Gln Val Thr Leu Lys Glu Ser Gly Pro Gly Ile Leu Gln Pro Ser Gln 
1               5                   10                  15      


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Asn Thr Ser 
            20                  25                  30          


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


Trp Leu Ala His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ser 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Ser Asn Gln Val 
65                  70                  75                  80  


Phe Leu Lys Ile Thr Ser Leu Asp Thr Ala Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Arg Ser His Phe Gly Asn Tyr Tyr Tyr Ala Met Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Ser Val Thr Val Thr Ser Ala Ser Thr Lys Gly 
        115                 120                 125             


Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 


Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 


Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     


Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         


Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             


Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 
    210                 215                 220                 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser Pro Gly 
    450         


<210>  35
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  1022C3 antibody light chain Chimeric (c) IgG1

<400>  35

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


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Phe Lys Leu Leu Ile 
        35                  40                  45              


Phe Tyr Thr Ser Arg Leu Gln Ser Gly Val Pro Ser Lys Tyr Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 
65                  70                  75                  80  


Glu Asp Ile Ala Ala Tyr Phe Cys Gln Gln Gly Lys Thr Leu Pro Leu 
                85                  90                  95      


Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  36
<211>  1359
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain Chimeric (c)

<400>  36
caggtgaccc tgaaggaaag cggacctggc attctgcagc catcacaaac actttcactg       60

acatgcagtt tttccggttt ttctctgaat accagcggga tgggggtcag ctggatccgc      120

cagcccagcg gtaagggact cgagtggctt gcccacatct attgggatga cgataagcgg      180

tacaacccct ccctcaaaag cagactgact attagtaaag acacttctag taatcaggtg      240

ttcttgaaga tcacctctct tgacacagcc gatactgcaa cttactactg cgctaggcga      300

tcccatttcg gcaactatta ctatgccatg gattattggg gccagggcac atctgtcaca      360

gttacctctg cttccaccaa gggcccttcc gtgttcccgc tagcccccag cagcaagagc      420

accagcggcg gcacagccgc cctgggctgc ctggtgaagg actacttccc cgagcccgtg      480

accgtgtcct ggaacagcgg agccctgacc tccggcgtgc acaccttccc cgccgtgctg      540

cagagcagcg gcctgtacag cctgagcagc gtggtgaccg tgcccagcag cagcctgggc      600

acccagacct acatctgtaa cgtgaaccac aagcccagca acaccaaggt ggacaagaga      660

gtggagccca agagctgtga caagacccac acctgccccc cctgcccagc ccccgagctg      720

ctgggcggac ccagcgtgtt cctgttcccc cccaagccca aggacaccct gatgatcagc      780

agaacccccg aggtgacctg tgtggtggtg gacgtgtccc acgaggaccc agaggtgaag      840

ttcaactggt acgtggacgg cgtggaggtg cacaacgcca agaccaagcc cagagaggag      900

cagtacaaca gcacctacag ggtggtgtcc gtgctgaccg tgctgcacca ggactggctg      960

aacggcaagg agtacaagtg taaggtgtcc aacaaggccc tgccagcccc aatcgaaaag     1020

accatcagca aggccaaggg ccagccaaga gagccccagg tgtacaccct gccacccagc     1080

agggaggaga tgaccaagaa ccaggtgtcc ctgacctgtc tggtgaaggg cttctaccca     1140

agcgacatcg ccgtggagtg ggagagcaac ggccagcccg agaacaacta caagaccacc     1200

cccccagtgc tggacagcga cggcagcttc ttcctgtaca gcaagctgac cgtggacaag     1260

agcagatggc agcagggcaa cgtgttcagc tgctccgtga tgcacgaggc cctgcacaac     1320

cactacaccc agaagagcct gagcctgtcc ccaggcaag                            1359


<210>  37
<211>  1356
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody heavy chain Chimeric (c) AlaAla

<400>  37
caggtgaccc tgaaggaaag cggacctggc attctgcagc catcacaaac actttcactg       60

acatgcagtt tttccggttt ttctctgaat accagcggga tgggggtcag ctggatccgc      120

cagcccagcg gtaagggact cgagtggctt gcccacatct attgggatga cgataagcgg      180

tacaacccct ccctcaaaag cagactgact attagtaaag acacttctag taatcaggtg      240

ttcttgaaga tcacctctct tgacacagcc gatactgcaa cttactactg cgctaggcga      300

tcccatttcg gcaactatta ctatgccatg gattattggg gccagggcac atctgtcaca      360

gttacctctg cttccaccaa gggcccaagc gtgttccccc tggcccccag cagcaagagc      420

accagcggcg gcacagccgc cctgggctgc ctggtgaagg actacttccc cgagcccgtg      480

accgtgtcct ggaacagcgg agccctgacc tccggcgtgc acaccttccc cgccgtgctg      540

cagagcagcg gcctgtacag cctgagcagc gtggtgaccg tgcccagcag cagcctgggc      600

acccagacct acatctgtaa cgtgaaccac aagcccagca acaccaaggt ggacaagaga      660

gtggagccca agagctgtga caagacccac acctgccccc cctgcccagc ccccgaggcg      720

gcgggcggac ccagcgtgtt cctgttcccc cccaagccca aggacaccct gatgatcagc      780

agaacccccg aggtgacctg tgtggtggtg gacgtgtccc acgaggaccc agaggtgaag      840

ttcaactggt acgtggacgg cgtggaggtg cacaacgcca agaccaagcc cagagaggag      900

cagtacaaca gcacctacag ggtggtgtcc gtgctgaccg tgctgcacca ggactggctg      960

aacggcaagg agtacaagtg taaggtgtcc aacaaggccc tgccagcccc aatcgaaaag     1020

accatcagca aggccaaggg ccagccaaga gagccccagg tgtacaccct gccacccagc     1080

agggaggaga tgaccaagaa ccaggtgtcc ctgacctgtc tggtgaaggg cttctaccca     1140

agcgacatcg ccgtggagtg ggagagcaac ggccagcccg agaacaacta caagaccacc     1200

cccccagtgc tggacagcga cggcagcttc ttcctgtaca gcaagctgac cgtggacaag     1260

agcagatggc agcagggcaa cgtgttcagc tgctccgtga tgcacgaggc cctgcacaac     1320

cactacaccc agaagagcct gagcctgtcc ccaggc                               1356


<210>  38
<211>  642
<212>  DNA
<213>  artificial

<220>
<223>  1022C3 antibody light chain Chimeric (c)

<400>  38
gacgtccaaa tgacacagac aacttcttcc ctgagcgctt ccttgggtga tcgagtgacc       60

attagttgca gagcaagcca ggacatctct tcatacctca actggtatca gcaaaaacct      120

gatggcacct tcaagctgct tattttctac accagtcggt tgcagtctgg cgttccatca      180

aagtattccg gctctgggag tggcaccgac tactccctca ccatcagcaa tcttgagcaa      240

gaggatatcg cagcctattt ctgccagcag ggaaagacac tccccctgac tttcggggct      300

gggaccaagc tggaactgaa acgtacggtg gccgctccca gcgtgttcat cttcccccca      360

agcgacgagc agctgaagag cggcaccgcc agcgtggtgt gtctgctgaa caacttctac      420

cccagggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagagcgg caacagccag      480

gagagcgtca ccgagcagga cagcaaggac tccacctaca gcctgagcag caccctgacc      540

ctgagcaagg ccgactacga gaagcacaag gtgtacgcct gtgaggtgac ccaccagggc      600

ctgtccagcc ccgtgaccaa gagcttcaac aggggcgagt gc                         642


