                                                   Sequence Listing

<110>  AC Immune S.A. and Genentech, Inc.
 
<120>  Safe and Functional Humanized Antibodies

<130>  12593-020-228

<140> To Be Determined
<141> To Be Determined

<150> 61/400,650
<151> 2010-07-30

<160>  22    

<170>  PatentIn version 3.3

<210>  1
<211>  10
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised heavy chain variable region  (CDR1)

<400>  1

Gly Phe Thr Phe Ser Ser Tyr Gly Met Ser 
1               5                   10  


<210>  2
<211>  17
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised heavy chain variable region  (CDR2)

<400>  2

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


Gly 
    


<210>  3
<211>  3
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised heavy chain variable region  (CDR3)

<400>  3

Gly Asp Tyr 
1           


<210>  4
<211>  16
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised light chain variable region  (CDR1)

<400>  4

Arg Ser Ser Gln Ser Leu Val Tyr Ser Asn Gly Asp Thr Tyr Leu His 
1               5                   10                  15      


<210>  5
<211>  7
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised light chain variable region  (CDR2)

<400>  5

Lys Val Ser Asn Arg Phe Ser 
1               5           


<210>  6
<211>  9
<212>  PRT
<213>  Mus musculus

<220>
<223>  MABT humanised light chain variable region  (CDR3)

<400>  6

Ser Gln Ser Thr His Val Pro Trp Thr 
1               5                   


<210>  7
<211>  112
<212>  PRT
<213>  Artificial sequence

<220>
<223>  artificial humanized MABT variable light chain

<400>  7

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr Ser 
            20                  25                  30          


Asn Gly Asp Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  8
<211>  219
<212>  PRT
<213>  artificial sequence

<220>
<223>  artificial humanized MABT light chain

<400>  8

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr Ser 
            20                  25                  30          


Asn Gly Asp Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


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


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


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  9
<211>  107
<212>  PRT
<213>  artificial sequence 

<220>
<223>  artificial humanized MABT light chain constant region

<400>  9

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


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


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  10
<211>  112
<212>  PRT
<213>  artificial sequence

<220>
<223>  artificial humanized MABT variable heavy chain

<400>  10

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


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


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


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


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


<210>  11
<211>  439
<212>  PRT
<213>  artificial sequence

<220>
<223>  artificial humanized MABT heavy chain

<400>  11

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


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


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


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


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


Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
        115                 120                 125             


Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
    130                 135                 140                 


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
145                 150                 155                 160 


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
                165                 170                 175     


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
            180                 185                 190         


Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
        195                 200                 205             


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


Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                245                 250                 255     


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
            260                 265                 270         


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
        275                 280                 285             


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
305                 310                 315                 320 


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                325                 330                 335     


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
            340                 345                 350         


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
        355                 360                 365             


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
    370                 375                 380                 


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
385                 390                 395                 400 


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
                405                 410                 415     


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
            420                 425                 430         


Leu Ser Leu Ser Leu Gly Lys 
        435                 


<210>  12
<211>  326
<212>  PRT
<213>  Homo sapiens

<220>
<223>  IG GAMMA-4 CHAIN C REGION modified

<400>  12

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
1               5                   10                  15      


Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
65                  70                  75                  80  


Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                165                 170                 175     


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
        195                 200                 205             


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 


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


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
    290                 295                 300                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
305                 310                 315                 320 


Leu Ser Leu Ser Leu Gly 
                325     



<210>  13
<211>  51
<212>  DNA
<213>  Mus musculus

<220>
<223> MABT humanised heavy chain variable region  (CDR2)

<400>  13
agcatcaata gtaatggtgg tagcacctat tatccagaca gtgtgaaggg c              51


<210>  14
<211>  9
<212>  DNA
<213>  Mus musculus

<220>
<223>  MABT humanised heavy chain variable region  (CDR3)

<400>  14
ggtgactac                                                              9


<210>  15
<211>  49
<212>  DNA
<213>  Mus musculus

<220>
<223>  MABT humanised light chain variable region  (CDR1)

<400>  15
agatctagtc agagccttgt atatagtaat ggagacacct atttacatt                 49


<210>  16
<211>  336
<212>  DNA
<213>  artificial sequence

<220>
<223>  artificial humanized MABT variable light chain

<400>  16
gatattgtga tgacccaatc tccactctcc ctgcctgtca ctcctggtga gcctgcctcc     60

atctcttgca gatctagtca gagccttgta tatagtaatg gagacaccta tttacattgg    120

tacctgcaga agccaggcca gtctccacag ctcctgatct acaaagtttc caaccgattt    180

tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc    240

agcagagtgg aggctgagga tgtgggagtt tattactgct ctcaaagtac acatgttcct    300

tggacgttcg gccaaggcac caaggtggaa atcaaa                              336



<210>  17
<211>  657
<212>  DNA
<213>  artificial sequence 

<220>
<223>  artificial humanized MABT light chain

<400>  17
gatattgtga tgacccaatc tccactctcc ctgcctgtca ctcctggtga gcctgcctcc     60

atctcttgca gatctagtca gagccttgta tatagtaatg gagacaccta tttacattgg    120

tacctgcaga agccaggcca gtctccacag ctcctgatct acaaagtttc caaccgattt    180

tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc    240

agcagagtgg aggctgagga tgtgggagtt tattactgct ctcaaagtac acatgttcct    300

tggacgttcg gccaaggcac caaggtggaa atcaaaagga ctgtggctgc accatctgtc    360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg    420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa    480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc    540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa    600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgt       657


<210>  18
<211>  321
<212>  DNA
<213>  Homo sapiens

<220>
<223> artificial humanized MABT light chain constant region

<400>  18
aggactgtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct     60

ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag    120

tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac    180

agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag    240

aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag    300

agcttcaaca ggggagagtg t                                              321


<210>  19
<211>  336
<212>  DNA
<213>  artificial sequence

<220>
<223>  artificial humanized MABT variable heavy chain

<400>  19
gaggtgcagc tggtcgagtc tgggggaggc ttagtgcagc ctggagggtc cctgagactc     60

tcctgtgcag cctctggatt cactttcagt agctatggca tgtcttgggt tcgccaggct    120

ccaggcaagg gtctcgaatt ggtcgcaagc atcaatagta atggtggtag cacctattat    180

ccagacagtg tgaagggccg attcaccatc tccagagaca atgccaagaa ctccctgtac    240

ctgcaaatga acagtctgag agctgaggac accgccgtgt attactgtgc aagtggtgac    300

tactggggcc aaggcaccac tgtcacagtc tcctca                              336



<210>  20
<211>  1317
<212>  DNA
<213>  artificial sequence 

<220>
<223>  artificial humanized MABT heavy chain

<400>  20
gaggtgcagc tggtcgagtc tgggggaggc ttagtgcagc ctggagggtc cctgagactc     60

tcctgtgcag cctctggatt cactttcagt agctatggca tgtcttgggt tcgccaggct    120

ccaggcaagg gtctcgaatt ggtcgcaagc atcaatagta atggtggtag cacctattat    180

ccagacagtg tgaagggccg attcaccatc tccagagaca atgccaagaa ctccctgtac    240

ctgcaaatga acagtctgag agctgaggac accgccgtgt attactgtgc aagtggtgac    300

tactggggcc aaggcaccac tgtcacagtc tcctcagctt ccaccaaggg cccatccgtc    360

ttccccctgg cgccctgctc cagatcgacc tccgagagca cagccgccct gggctgcctg    420

gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc    480

ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg    540

gtgaccgtgc cctccagcag cttgggcacg aagacctaca cctgcaacgt agatcacaag    600

cccagcaaca ccaaggtgga caagagagtt gagtccaaat atggtccccc gtgtccccca    660

tgcccagcac ctgagttcct ggggggacca tcagtcttcc tgttcccccc aaaacccaag    720

gacactctca tgatctcccg gacccctgag gtcacgtgcg tggtggtgga cgtgagccag    780

gaagaccccg aggtccagtt caactggtac gtggatggcg tggaggtgca taatgccaag    840

acaaagccgc gggaggagca gttcaacagc acgtaccgtg tggtcagcgt cctcaccgtc    900

ctgcaccagg actggctgaa cggcaaggag tacaagtgca aggtctccaa caaaggcctc    960

ccgtcctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga gccacaggtg   1020

tacaccctgc ccccatccca ggaggagatg accaagaacc aggtcagcct gacctgcctg   1080

gtcaaaggct tctaccccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag   1140

aacaactaca agaccacgcc tcccgtcctc gattccgacg gctccttctt cctctacagc   1200

aggctaaccg tggacaagag caggtggcag gaggggaatg tcttctcatg ctccgtgatg   1260

catgaggctc tgcacaacca ctacacacag aagagcctct ccctgtctct gggtaaa      1317


<210>  21
<211>  981
<212>  DNA
<213>  Homo sapiens

<220>
<223> artificial humanized MABT heavy chain constant region

<400>  21
gcttccacca agggcccatc cgtcttcccc ctggcgccct gctccagatc gacctccgag     60

agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg    120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca    180

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc    240

tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc    300

aaatatggtc ccccgtgtcc cccatgccca gcacctgagt tcctgggggg accatcagtc    360

ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg    420

tgcgtggtgg tggacgtgag ccaggaagac cccgaggtcc agttcaactg gtacgtggat    480

ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac    540

cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag    600

tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa    660

gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag    720

aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag    780

tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt cctcgattcc    840

gacggctcct tcttcctcta cagcaggcta accgtggaca agagcaggtg gcaggagggg    900

aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc    960

ctctccctgt ctctgggtaa a                                              981


<210>  22
<211>  5
<212>  PRT
<213>  Homo sapiens

<220>
<223> Typical amino acid sequence preceding HCDR2

<400>  22
Leu Glu Trp Ile Gly
1               5
