                         SEQUENCE LISTING

<110>  Novartis AG
       Skegro, Darko
       Irigaray, Sebastien
       Ebersbach, Hilmar
 
<120>  ANTI-TNF-ALPHA ANTIBODIES

<130>  PAT058234-PCT

<140>  Herewith
<141>  Herewith

<150>  62/781668
<151>  2018-12-19

<160>  29    

<170>  PatentIn version 3.5

<210>  1
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR1 adalimumab

<400>  1

Gly Phe Thr Phe Asp Asp Tyr Ala 
1               5               


<210>  2
<211>  8
<212>  PRT
<213>  artificial sequence

<220>
<223>  HCDR2 adalimumab and Variant 4 and Variant 40

<400>  2

Ile Thr Trp Asn Ser Gly His Ile 
1               5               


<210>  3
<211>  14
<212>  PRT
<213>  artificial sequence

<220>
<223>  HCDR3 adalimumab and Variant 4 and Variant 40

<400>  3

Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Tyr 
1               5                   10                  


<210>  4
<211>  121
<212>  PRT
<213>  artificial sequence

<220>
<223>  VH adalimumab

<400>  4

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  5
<211>  363
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA VH adaliumumab

<400>  5
gaagtgcagc tggtggaatc tggcggagga ctggttcagc ctggcagaag cctgagactg       60

tcttgtgccg ccagcggctt caccttcgat gattatgcca tgcactgggt ccgacaggcc      120

cctggaaaag gacttgaatg ggtgtccgcc atcacctgga acagcggcca catcgattac      180

gccgatagcg tggaaggccg gttcaccatc agcagagaca acgccaagaa cagcctgtac      240

ctccagatga actccctgag agccgaggat accgccgtgt actattgcgc caaggtgtcc      300

tacctgagca ccgcctcttc tctggattac tggggacagg gcaccctggt cacagtgagc      360

tca                                                                    363


<210>  6
<211>  451
<212>  PRT
<213>  artificial sequence

<220>
<223>  Heavy chain adaliumumab

<400>  6

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


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


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


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


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  7
<211>  1353
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA Heavy chain adaliumumab

<400>  7
gaagtgcagc tggtggaatc tggcggagga ctggttcagc ctggcagaag cctgagactg       60

tcttgtgccg ccagcggctt caccttcgat gattatgcca tgcactgggt ccgacaggcc      120

cctggaaaag gacttgaatg ggtgtccgcc atcacctgga acagcggcca catcgattac      180

gccgatagcg tggaaggccg gttcaccatc agcagagaca acgccaagaa cagcctgtac      240

ctccagatga actccctgag agccgaggat accgccgtgt actattgcgc caaggtgtcc      300

tacctgagca ccgcctcttc tctggattac tggggacagg gcaccctggt cacagtgagc      360

tcagctagca ccaagggccc cagcgtgttc cccctggcgc ccagcagcaa gagcaccagc      420

ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc agtgaccgtg      480

tcctggaaca gcggagccct gacctccggc gtgcacacct tccccgccgt gctgcagagc      540

agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag      600

acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa gagagtggag      660

cccaagagct gcgacaagac ccacacctgc cccccctgtc ctgcccctga actgctgggc      720

ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc      780

cccgaagtga cctgcgtggt ggtggacgtg tcccacgagg accctgaagt gaagttcaat      840

tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagtac      900

aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc      960

aaagagtaca agtgcaaagt ctccaacaag gccctgcctg cccccatcga gaaaaccatc     1020

agcaaggcca agggccagcc ccgcgagccc caggtgtaca cactgccccc cagccgggac     1080

gagctgacca agaaccaggt gtccctgacc tgcctggtca agggcttcta ccccagcgat     1140

atcgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct     1200

gtgctggaca gcgacggctc attcttcctg tacagcaagc tgaccgtgga caagtcccgg     1260

tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac     1320

acccagaagt ccctgagcct gagccccggc aaa                                  1353


<210>  8
<211>  6
<212>  PRT
<213>  artificial sequence

<220>
<223>  LCDR1 adalimumab and Variant 4 and variant 40

<400>  8

Gln Gly Ile Arg Asn Tyr 
1               5       


<210>  9
<211>  3
<212>  PRT
<213>  artificial sequence

<220>
<223>  LCDR2 adalimumab and Variant 4 and variant 40

<400>  9

Ala Ala Ser 
1           


<210>  10
<211>  9
<212>  PRT
<213>  artificial sequence

<220>
<223>  LCDR3 adaliumumab and Variant 4 and variant 40

<400>  10

Gln Arg Tyr Asn Arg Ala Pro Tyr Thr 
1               5                   


<210>  11
<211>  107
<212>  PRT
<213>  artificial sequence

<220>
<223>  VL adalimumab and Variant 4

<400>  11

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


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


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


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


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


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  12
<211>  321
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA VL adalimumab and Variant 4

<400>  12
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc       60

atcacatgtc gggccagcca gggcatcaga aactacctgg cctggtatca gcagaagccc      120

ggaaaggccc ctaagctgct gatctatgcc gcctctacac tccagagcgg cgtgccaagc      180

agattttctg gcagcggctc tggcaccgac ttcaccctga ccatttctag cctccagcca      240

gaggacgtgg ccacctacta ctgccagaga tacaacagag ccccttacac cttcggccag      300

ggcaccaagg ttgagatcaa g                                                321


<210>  13
<211>  214
<212>  PRT
<213>  artificial sequence

<220>
<223>  light chain adalimumab and Variant 4

<400>  13

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


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


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


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


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


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 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>  14
<211>  642
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA light chain adalimumab and Variant 4

<400>  14
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc       60

atcacatgtc gggccagcca gggcatcaga aactacctgg cctggtatca gcagaagccc      120

ggaaaggccc ctaagctgct gatctatgcc gcctctacac tccagagcgg cgtgccaagc      180

agattttctg gcagcggctc tggcaccgac ttcaccctga ccatttctag cctccagcca      240

gaggacgtgg ccacctacta ctgccagaga tacaacagag ccccttacac cttcggccag      300

ggcaccaagg ttgagatcaa gcgtacggtg gcagctccgt ctgttttcat ctttccacct      360

agcgacgagc aactcaaaag tggtacagca tccgtggttt gtctgctgaa caatttttac      420

cccagggagg ctaaggtcca gtggaaagtc gataacgctc ttcagtctgg caacagtcag      480

gagagcgtca cagagcagga ctctaaggat agcacttata gtctgtcctc cacgctgaca      540

ctgtctaaag cggattatga gaagcacaag gtttacgcct gtgaggtaac gcaccaagga      600

ctctcctccc cagttaccaa atctttcaac agaggagaat gt                         642


<210>  15
<211>  8
<212>  PRT
<213>  artificial sequence

<220>
<223>  HCDR1 Variant 4 and Variant 40

<400>  15

Gly Phe Thr Phe Asp Asp Ser Ala 
1               5               


<210>  16
<211>  121
<212>  PRT
<213>  artificial sequence

<220>
<223>  VH variant 4 and Variant 40

<400>  16

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  17
<211>  363
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA VH Variant 4 and Variant 40

<400>  17
gaagtgcagc tggtggaatc tggcggagga ctggttcagc ctggcagaag cctgagactg       60

tcttgtgccg ccagcggctt caccttcgat gattctgcca tgcactgggt ccgacaggcc      120

cctggaaaag gacttgaatg ggtgtccgcc atcacctgga acagcggcca catcgattac      180

gccgatagcg tggaaggccg gttcaccatc agcagagaca acgccaagaa cagcctgtac      240

ctccagatga actccctgag agccgaggat accgccgtgt actattgcgc caaggtgtcc      300

tacctgagca ccgcctcttc tctggattac tggggacagg gcaccctggt cacagtgagc      360

tca                                                                    363


<210>  18
<211>  451
<212>  PRT
<213>  artificial sequence

<220>
<223>  Heavy chain Variant 4 and variant 40

<400>  18

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Ser Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


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


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


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


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  19
<211>  1353
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA Heavy chain variant 4 and variant 40

<400>  19
gaagtgcagc tggtggaatc tggcggagga ctggttcagc ctggcagaag cctgagactg       60

tcttgtgccg ccagcggctt caccttcgat gattctgcca tgcactgggt ccgacaggcc      120

cctggaaaag gacttgaatg ggtgtccgcc atcacctgga acagcggcca catcgattac      180

gccgatagcg tggaaggccg gttcaccatc agcagagaca acgccaagaa cagcctgtac      240

ctccagatga actccctgag agccgaggat accgccgtgt actattgcgc caaggtgtcc      300

tacctgagca ccgcctcttc tctggattac tggggacagg gcaccctggt cacagtgagc      360

tcagctagca ccaagggccc cagcgtgttc cccctggcgc ccagcagcaa gagcaccagc      420

ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc agtgaccgtg      480

tcctggaaca gcggagccct gacctccggc gtgcacacct tccccgccgt gctgcagagc      540

agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag      600

acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa gagagtggag      660

cccaagagct gcgacaagac ccacacctgc cccccctgtc ctgcccctga actgctgggc      720

ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc      780

cccgaagtga cctgcgtggt ggtggacgtg tcccacgagg accctgaagt gaagttcaat      840

tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagtac      900

aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc      960

aaagagtaca agtgcaaagt ctccaacaag gccctgcctg cccccatcga gaaaaccatc     1020

agcaaggcca agggccagcc ccgcgagccc caggtgtaca cactgccccc cagccgggac     1080

gagctgacca agaaccaggt gtccctgacc tgcctggtca agggcttcta ccccagcgat     1140

atcgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct     1200

gtgctggaca gcgacggctc attcttcctg tacagcaagc tgaccgtgga caagtcccgg     1260

tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac     1320

acccagaagt ccctgagcct gagccccggc aaa                                  1353


<210>  20
<211>  107
<212>  PRT
<213>  artificial sequence

<220>
<223>  VL Variant 40

<400>  20

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


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


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


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


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


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  21
<211>  321
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA VL Variant 40

<400>  21
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc       60

atcacatgtc gggccagcca gggcatcaga aactacctgg cctggtatca gcagaagccc      120

ggaaaggccc ctaagctgct gatctatgcc gcctctacac tccagacagg cgtgccaagc      180

agattttctg gcagcggctc tggcaccgac ttcaccctga ccatttctag cctccagcca      240

gaggacgtgg ccacctacta ctgccagaga tacaacagag ccccttacac cttcggccag      300

ggcaccaagg ttgagatcaa g                                                321


<210>  22
<211>  214
<212>  PRT
<213>  artificial sequence

<220>
<223>  Light chain variant 40

<400>  22

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


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


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


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


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


Glu Asp Val Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 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>  23
<211>  642
<212>  DNA
<213>  artificial sequence

<220>
<223>  DNA Light chain variant 40

<400>  23
gatatccaga tgacacagag ccctagcagc ctgtctgcct ctgtgggcga tagagtgacc       60

atcacatgtc gggccagcca gggcatcaga aactacctgg cctggtatca gcagaagccc      120

ggaaaggccc ctaagctgct gatctatgcc gcctctacac tccagacagg cgtgccaagc      180

agattttctg gcagcggctc tggcaccgac ttcaccctga ccatttctag cctccagcca      240

gaggacgtgg ccacctacta ctgccagaga tacaacagag ccccttacac cttcggccag      300

ggcaccaagg ttgagatcaa gcgtacggtg gcagctccgt ctgttttcat ctttccacct      360

agcgacgagc aactcaaaag tggtacagca tccgtggttt gtctgctgaa caatttttac      420

cccagggagg ctaaggtcca gtggaaagtc gataacgctc ttcagtctgg caacagtcag      480

gagagcgtca cagagcagga ctctaaggat agcacttata gtctgtcctc cacgctgaca      540

ctgtctaaag cggattatga gaagcacaag gtttacgcct gtgaggtaac gcaccaagga      600

ctctcctccc cagttaccaa atctttcaac agaggagaat gt                         642


<210>  24
<211>  36
<212>  PRT
<213>  artificial sequence

<220>
<223>  VK1-13 FR3

<400>  24

Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 
1               5                   10                  15      


Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 
            20                  25                  30          


Thr Tyr Tyr Cys 
        35      


<210>  25
<211>  36
<212>  PRT
<213>  artificial sequence

<220>
<223>  VK1-33 FR3

<400>  25

Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 
1               5                   10                  15      


Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala 
            20                  25                  30          


Thr Tyr Tyr Cys 
        35      


<210>  26
<211>  121
<212>  PRT
<213>  artificial sequence

<220>
<223>  Generic Sequence Variant VH


<220>
<221>  31_Xaa
<222>  (31)..(31)
<223>  X may be D (Asp), S (Ser), or N (Asn)

<220>
<221>  32_Xaa
<222>  (32)..(32)
<223>  X may be Y (Tyr), S (Ser), or F (Phe)

<220>
<221>  58_Xaa
<222>  (58)..(58)
<223>  X may be I (Ile) or T (Thr)

<220>
<221>  107_Xaa
<222>  (107)..(107)
<223>  X may be S (Ser) or A (Ala)

<400>  26

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Xaa Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  27
<211>  451
<212>  PRT
<213>  artificial sequence

<220>
<223>  Generic Variant Heavy Chain


<220>
<221>  Xaa_31
<222>  (31)..(31)
<223>  X may be D (Asp), S (Ser), or N (Asn)

<220>
<221>  Xaa_32
<222>  (32)..(32)
<223>  X may be Y (Tyr), S (Ser), or F (Phe)

<220>
<221>  Xaa_58
<222>  (58)..(58)
<223>  X may be I (Ile) or T (Thr)

<220>
<221>  Xaa_107
<222>  (107)..(107)
<223>  X may be S (Ser) or A (Ala)

<400>  27

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 
1               5                   10                  15      


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


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


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


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


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


Ala Lys Val Ser Tyr Leu Ser Thr Ala Ser Xaa Leu Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


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


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


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


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  28
<211>  108
<212>  PRT
<213>  artificial sequence

<220>
<223>  Generic Variant VL


<220>
<221>  Xaa_28
<222>  (28)..(28)
<223>  X may be G (Gly) or S (Ser)

<220>
<221>  Xaa_53
<222>  (53)..(53)
<223>  X may be T (Thr), S (Ser) or N (Asn)

<220>
<221>  Xaa_54
<222>  (54)..(54)
<223>  X may be L (Leu) or R (Arg)

<220>
<221>  Xaa_55
<222>  (55)..(55)
<223>  X may be Q (Gln) or E (Glu)

<220>
<221>  Xaa_56
<222>  (56)..(56)
<223>  X may be S (Ser) or T (Thr)

<220>
<221>  Xaa_83
<222>  (83)..(83)
<223>  X may be V (Val), F (Phe) or I (Ile)

<400>  28

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


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


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


Tyr Ala Ala Ser Xaa Xaa Xaa Xaa Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Xaa Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105             


<210>  29
<211>  214
<212>  PRT
<213>  artificial sequence

<220>
<223>  Generic Variant Light Chain


<220>
<221>  Xaa_28
<222>  (28)..(28)
<223>  X may be G (Gly) or S (Ser)

<220>
<221>  Xaa_53
<222>  (53)..(53)
<223>  X may be T (Thr), S (Ser), or N (Asn)

<220>
<221>  Xaa_54
<222>  (54)..(54)
<223>  X may be L (Leu) or R (Arg)

<220>
<221>  Xaa_55
<222>  (55)..(55)
<223>  X may be Q (Gln) or E (Glu)

<220>
<221>  Xaa_56
<222>  (56)..(56)
<223>  X may be S (Ser) or T (Thr)

<220>
<221>  Xaa_83
<222>  (83)..(83)
<223>  X may be V (Val), F (Phe) or I (Ile)

<400>  29

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


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


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


Tyr Ala Ala Ser Xaa Xaa Xaa Xaa Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Xaa Ala Thr Tyr Tyr Cys Gln Arg Tyr Asn Arg Ala Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 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                 


