                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Multispecific domain exchanged common variable light chain 
       antibodies

<130>  P31793-WO

<150>  EP 13188283.9
<151>  2013-10-11

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  1374
<212>  DNA
<213>  Artificial

<220>
<223>  nucleotide sequence of modified heavy chain CH3-CH2-CH1-VL, 
       wherein VL is a variable domain of a common light chain (CLC-Fc 
       cross-Mab)

<400>  1
atgggatgga gctgtatcat cctcttcttg gtagcaacag ctaccggtgt gcattccgac       60

atccagatga cccagagccc cagcagcctg agcgccagcg tgggcgacag agtgaccatc      120

acctgcagcg ccagccaggg catccggaac tacctgaact ggtatcagca gaagcccggc      180

aaggccccca agctgctgat ctactacacc agcagcctgc acagcggcgt gcctagccgg      240

tttagcggca gcggctccgg caccgacttc accctgacca ttagctccct gcagcccgag      300

gacttcgcca cctactactg ccagcagtac agcaagctgc cctggacctt cggccaggga      360

acaaaggtgg agatcaagag ctccgctagc accaagggcc catcggtctt ccccctggca      420

ccctcctcca agagcacctc tgggggcaca gcggccctgg gctgcctggt caaggactac      480

ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc      540

ttcccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc      600

tccagcagct tgggcaccca gacctacatc tgcaacgtga atcacaagcc cagcaacacc      660

aaggtggaca agaaagttga gcccaaatct tgtgacaaaa ctcacacatg cccaccgtgc      720

ccagcacctg aactcctggg gggaccgtca gtcttcctct tccccccaaa acccaaggac      780

accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa      840

gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca      900

aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg      960

caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca     1020

gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac     1080

accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc     1140

aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac     1200

aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag     1260

ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat     1320

gaggctctgc acaaccacta cacgcagaag agcctctccc tgtctccggg taaa           1374


<210>  2
<211>  738
<212>  DNA
<213>  Artificial

<220>
<223>  nucleotide sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 2A11-CL (kappa))

<400>  2
atgggctgga gctgcatcat cctgttcctg gtggccaccg ccaccggcgt gcattccgag       60

gtgcagctgc tggagagcgg cggcggcctg gtgcagcccg gcggcagcct gaggctgagc      120

tgcgccgcca gcggcttcac cttcagcagc tacgccatga gctgggtgag gcaggccccc      180

ggcaagggcc tggagtgggt gagcgccatc agcggcagcg gcggcagcac ctactacgcc      240

gacagcgtga agggcaggtt caccatcagc agggacaaca gcaagaacac cctgtacctg      300

cagatgaaca gcctgagggc cgaggacacc gccgtgtact actgcgccag gggcccctac      360

ggcaggtacg ccgccctgga ctactggggc cagggcaccc tggtgaccgt gagcagcgct      420

agcgtggccg ctcccagcgt gttcatcttc ccacccagcg acgagcagct gaagtccggc      480

acagccagcg tggtgtgcct gctgaacaac ttctaccccc gcgaggccaa ggtgcagtgg      540

aaggtggaca acgccctgca gagcggcaac agccaggaat ccgtgaccga gcaggacagc      600

aaggactcca cctacagcct gagcagcacc ctgaccctga gcaaggccga ctacgagaag      660

cacaaggtgt acgcctgcga agtgacccac cagggcctgt ccagccccgt gaccaagagc      720

ttcaaccggg gcgagtgc                                                    738


<210>  3
<211>  744
<212>  DNA
<213>  Artificial

<220>
<223>  nucleotide sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 8E11 -CL (kappa))

<400>  3
atgggctgga gctgcatcat cctgttcctg gtggccaccg ccaccggcgt gcattccgag       60

gtgcaattgt tggagtctgg gggaggcttg gtacagcctg gggggtccct gagactctcc      120

tgtgcagcct ccggattcac ctttagcagt tatgccatga gctgggtccg ccaggctcca      180

gggaaggggc tggagtgggt ctcagctatt agtggtagtg gtggtagcac atactacgca      240

gactccgtga agggccggtt caccatctcc agagacaatt ccaagaacac gctgtatctg      300

cagatgaaca gcctgagagc cgaggacacg gccgtatatt actgtgcgaa agactcttct      360

tcttggtact cctacgcttt cgactactgg ggccaaggaa ccctggtcac cgtctcgagt      420

gctagcgtgg ccgctcccag cgtgttcatc ttcccaccca gcgacgagca gctgaagtcc      480

ggcacagcca gcgtggtgtg cctgctgaac aacttctacc cccgcgaggc caaggtgcag      540

tggaaggtgg acaacgccct gcagagcggc aacagccagg aatccgtgac cgagcaggac      600

agcaaggact ccacctacag cctgagcagc accctgaccc tgagcaaggc cgactacgag      660

aagcacaagg tgtacgcctg cgaagtgacc caccagggcc tgtccagccc cgtgaccaag      720

agcttcaacc ggggcgagtg ctga                                             744


<210>  4
<211>  729
<212>  DNA
<213>  Artificial

<220>
<223>  nucleotide sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 21C11 -CL (kappa))

<400>  4
atgggctgga gctgcatcat cctgttcctg gtggccaccg ccaccggcgt gcattcccag       60

gtgcaattgg tgcagtctgg ggctgaggtg aagaagcctg ggtcctcggt gaaggtctcc      120

tgcaaggcct ccggaggcac attcagcagc tacgctataa gctgggtgcg acaggcccct      180

ggacaagggc tcgagtggat gggaaggatc atccctatct ttggtacagc aaactacgca      240

cagaagttcc agggcagggt caccattact gcagacaaat ccacgagcac agcctacatg      300

gagctgagca gcctgagatc tgaggacacc gccgtgtatt actgtgcgag agaaggtttc      360

tacatcgact actggggcca agggaccacc gtgaccgtct cctcagctag cgtggccgct      420

cccagcgtgt tcatcttccc acccagcgac gagcagctga agtccggcac agccagcgtg      480

gtgtgcctgc tgaacaactt ctacccccgc gaggccaagg tgcagtggaa ggtggacaac      540

gccctgcaga gcggcaacag ccaggaatcc gtgaccgagc aggacagcaa ggactccacc      600

tacagcctga gcagcaccct gaccctgagc aaggccgact acgagaagca caaggtgtac      660

gcctgcgaag tgacccacca gggcctgtcc agccccgtga ccaagagctt caaccggggc      720

gagtgctga                                                              729


<210>  5
<211>  735
<212>  DNA
<213>  Artificial

<220>
<223>  nucleotide sequence of modified light chain VH2-Clambda wherein 
       VH2 is the variable heavy chain domain from an antibody which 
       binds to a second antigen (anti-FAP VH2 3C6 -CL (lambda))

<400>  5
atgggatgga gctgtatcat cctcttcttg gtagcaacag ctaccggtgt gcattccgag       60

gtgcagctgc tggagagcgg cggcggcctg gtgcagcccg gcggcagcct gaggctgagc      120

tgcgccgcca gcggcttcac cttcagcagc tacgccatga gctgggtgag gcaggccccc      180

ggcaagggcc tggagtgggt gagcgccatc agcggcagcg gcggcagcac ctactacgcc      240

gacagcgtga agggcaggtt caccatcagc agggacaaca gcaagaacac cctgtacctg      300

cagatgaaca gcctgagggc cgaggacacc gccgtgtact actgcgccaa gagcgtggtg      360

tacagctacg accccggctt cgactactgg ggccagggca ccctggtgac cgtgtccgga      420

cagcccaagg ccgcccccag cgtgaccctg ttccccccca gcagcgagga gctgcaggcc      480

aacaaggcca ccctggtgtg cctgatcagc gacttctacc ccggcgccgt gaccgtggcc      540

tggaaggccg acagcagccc cgtgaaggcc ggcgtggaga ccaccacccc cagcaagcag      600

agcaacaaca agtacgccgc cagcagctac ctgagcctga cccccgagca gtggaagagc      660

cacaggagct acagctgcca ggtgacccac gagggcagca ccgtggagaa gaccgtggcc      720

cccaccgagt gcagc                                                       735


<210>  6
<211>  458
<212>  PRT
<213>  Artificial

<220>
<223>  amino acid sequence of modified heavy chain CH3-CH2-CH1-VL, 
       wherein VL is a variable domain of a common light chain (CLC-Fc 
       cross-Mab)

<400>  6

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


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


Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Gly Ile 
        35                  40                  45              


Arg Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
    50                  55                  60                  


Leu Leu Ile Tyr Tyr Thr Ser Ser Leu His Ser Gly Val Pro Ser Arg 
65                  70                  75                  80  


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
                85                  90                  95      


Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Lys 
            100                 105                 110         


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


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


Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
145                 150                 155                 160 


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


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
            180                 185                 190         


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
        195                 200                 205             


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
    210                 215                 220                 


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


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                245                 250                 255     


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


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


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
    290                 295                 300                 


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
305                 310                 315                 320 


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                325                 330                 335     


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
            340                 345                 350         


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


Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
    370                 375                 380                 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
385                 390                 395                 400 


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


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
            420                 425                 430         


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
        435                 440                 445             


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455             


<210>  7
<211>  246
<212>  PRT
<213>  Artificial

<220>
<223>  amino acid sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 2A11-CL (kappa))

<400>  7

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


Val His Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 
            20                  25                  30          


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 
        35                  40                  45              


Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Gly Pro Tyr Gly Arg Tyr Ala Ala Leu Asp Tyr 
        115                 120                 125             


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala Ala 
    130                 135                 140                 


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
145                 150                 155                 160 


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
                165                 170                 175     


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
            180                 185                 190         


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
        195                 200                 205             


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
    210                 215                 220                 


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


Phe Asn Arg Gly Glu Cys 
                245     


<210>  8
<211>  247
<212>  PRT
<213>  Artificial

<220>
<223>  amino acid sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 8E11 -CL (kappa))

<400>  8

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


Val His Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 
            20                  25                  30          


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 
        35                  40                  45              


Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Lys Asp Ser Ser Ser Trp Tyr Ser Tyr Ala Phe Asp 
        115                 120                 125             


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Val Ala 
    130                 135                 140                 


Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
145                 150                 155                 160 


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


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
            180                 185                 190         


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
        195                 200                 205             


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
    210                 215                 220                 


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


Ser Phe Asn Arg Gly Glu Cys 
                245         


<210>  9
<211>  242
<212>  PRT
<213>  Artificial

<220>
<223>  amino acid sequence of modified light chain comprising a 
       polypeptide consisting of Ckappa-VH1-Ckappa wherein VH1 is the 
       variable heavy chain domain from an antibody which binds to a 
       first antigen (anti-DR5 VH1 21C11 -CL (kappa))

<400>  9

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


Val His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe 
        35                  40                  45              


Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Met Gly Arg Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala 
65                  70                  75                  80  


Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser 
                85                  90                  95      


Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Glu Gly Phe Tyr Ile Asp Tyr Trp Gly Gln Gly 
        115                 120                 125             


Thr Thr Val Thr Val Ser Ser Ala Ser Val Ala Ala Pro Ser Val Phe 
    130                 135                 140                 


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


Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 
                165                 170                 175     


Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 
            180                 185                 190         


Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 
        195                 200                 205             


Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 
    210                 215                 220                 


Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 
225                 230                 235                 240 


Glu Cys 
        


<210>  10
<211>  245
<212>  PRT
<213>  Artificial

<220>
<223>  amino acid sequence of modified light chain VH2-Clambda wherein 
       VH2 is the variable heavy chain domain from an antibody which 
       binds to a second antigen (anti-FAP VH2 3C6 -CL (lambda))

<400>  10

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


Val His Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln 
            20                  25                  30          


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 
        35                  40                  45              


Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Lys Ser Val Val Tyr Ser Tyr Asp Pro Gly Phe Asp 
        115                 120                 125             


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Gly Gln Pro Lys Ala 
    130                 135                 140                 


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


Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala 
                165                 170                 175     


Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val 
            180                 185                 190         


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


Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr 
    210                 215                 220                 


Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala 
225                 230                 235                 240 


Pro Thr Glu Cys Ser 
                245 


