                         SEQUENCE LISTING

<110>  Akeso Biopharma, Inc.
       Li, Baiyong
       Xia, Yu
       Wang, Zhongmin
       Zhang, Peng
       Pang, Xinghua
 
<120>  ANTI-CTLA4 ANTIBODIES

<130>  24359

<150>  PCT/CN2016/096357
<151>  2016-08-23

<160>  36    

<170>  PatentIn version 3.5

<210>  1
<211>  364
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CTLA4-mFc fusion protein

<400>  1

Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly 
1               5                   10                  15      


Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu 
            20                  25                  30          


Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val 
        35                  40                  45              


Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp 
    50                  55                  60                  


Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile 
65                  70                  75                  80  


Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu 
                85                  90                  95      


Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln 
            100                 105                 110         


Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Glu Asn Leu 
        115                 120                 125             


Tyr Phe Gln Gly Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys 
    130                 135                 140                 


Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe 
145                 150                 155                 160 


Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val 
                165                 170                 175     


Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile 
            180                 185                 190         


Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr 
        195                 200                 205             


His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro 
    210                 215                 220                 


Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val 
225                 230                 235                 240 


Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro 
                245                 250                 255     


Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu 
            260                 265                 270         


Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp 
        275                 280                 285             


Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr 
    290                 295                 300                 


Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser 
305                 310                 315                 320 


Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu 
                325                 330                 335     


Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His 
            340                 345                 350         


His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 
        355                 360                 


<210>  2
<211>  1092
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CTLA4-mFC fusion

<400>  2
gcaatgcatg tcgcacagcc tgcagtggtc ctggcaagct ccaggggaat cgctagcttc       60

gtgtgcgaat acgcttcccc aggcaaggca accgaggtcc gggtgacagt cctgagacag      120

gccgacagcc aggtgacaga agtctgcgcc gctacttata tgatgggcaa cgagctgacc      180

tttctggacg atagcatttg taccgggaca tctagtggaa accaagtgaa tctgaccatc      240

cagggcctgc gcgctatgga cacagggctg tacatttgta aagtggagct gatgtatccc      300

cctccatact atctgggaat cggcaacggg acccagatct acgtgattga tcctgaacca      360

tgccccgact ccgatgagaa tctgtatttc cagggaccac gaggccccac aattaagcca      420

tgtccccctt gcaaatgtcc tgcaccaaac ctgctgggag gaccaagcgt gttcatcttt      480

ccacccaaga tcaaggacgt gctgatgatc tcactgagcc ccattgtgac ctgcgtggtc      540

gtggacgtga gcgaggacga tcctgatgtg cagatcagtt ggttcgtcaa caatgtggaa      600

gtccacacag ctcagactca gacccatagg gaggattaca atagtactct gcgcgtcgtg      660

tcagcactgc ccattcagca ccaggactgg atgagcggca aggagttcaa gtgcaaagtg      720

aacaacaagg atctgcccgc acctatcgag agaactattt ccaagcctaa agggtctgtg      780

agggccccac aggtgtatgt cctgcctcca cccgaggaag agatgactaa gaaacaggtg      840

acactgactt gtatggtcac cgacttcatg cccgaagata tctacgtgga gtggactaac      900

aatgggaaga ccgaactgaa ctataaaaat acagagcctg tgctggactc agatggaagc      960

tactttatgt atagcaagct gcgagtggaa aagaaaaact gggtcgagcg gaacagctac     1020

tcttgtagtg tggtccacga agggctgcat aatcaccaca ccactaaatc attctcccga     1080

actccaggca aa                                                         1092


<210>  3
<211>  372
<212>  DNA
<213>  Mus musculus

<400>  3
caggtcaagc tgcaggagtc tggacctgag ctggtgaagc ctggagcttc aatgaagata       60

tcctgcaagg cttctggtta ctcattcact ggctacacca tgaactgggt gaagcagagc      120

catggaaaga accttgaatg gattggactt attaatcctt acaataatat tactaactac      180

aaccagaagt tcatgggcaa ggccacattt actgtagaca agtcatccag cacagcctac      240

atggaactcc tcagactgac atctgaagac tctggagtct atttctgtgc aagactcgac      300

tataggtctt attggggcca agggactctg gtcactgtct ctgcagccaa aacgacaccc      360

ccatctgtct at                                                          372


<210>  4
<211>  115
<212>  PRT
<213>  Mus musculus

<400>  4

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


Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 
            20                  25                  30          


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


Gly Leu Ile Asn Pro Tyr Asn Asn Ile Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Met Gly Lys Ala Thr Phe Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Leu Arg Leu Thr Ser Glu Asp Ser Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  5
<211>  378
<212>  DNA
<213>  Mus musculus

<400>  5
caggctgttg tgactcagga atctgcactc accacatcac ctggtgaaac agtcacactc       60

acttgtcgct caagtactgg ggctgttaca actagtaact ttgccaactg ggtccaagaa      120

aaaccagatc atttattcac tagtctaata ggtggtacca acaaccgagc tccaggtgtt      180

cctgccagat tctcaggctc cctgattgga gacaaggctg ccctcaccat cacaggggca      240

cagactgagg atgaggcaat atatttctgt gctctatggt acagcaacca ttgggtgttc      300

ggtggaggaa ccaaactgac tgtcctaggc cagcccaagt cttcgccatc agtcaccctg      360

tttcaagggc aattctgc                                                    378


<210>  6
<211>  126
<212>  PRT
<213>  Mus musculus

<400>  6

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


Thr Val Thr Leu Thr Cys Arg Ser Ser Thr Gly Ala Val Thr Thr Ser 
            20                  25                  30          


Asn Phe Ala Asn Trp Val Gln Glu Lys Pro Asp His Leu Phe Thr Ser 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Asn Arg Ala Pro Gly Val Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Ile Gly Asp Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  


Gln Thr Glu Asp Glu Ala Ile Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


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


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


<210>  7
<211>  345
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized light chain variable region of 4G10H1L1

<400>  7
caggtgcagc tggtggagtc tggggccgag ctggtgaagc ccggcgcctc catgaagatc       60

tcttgcaagg ccagcggata cagtttcact ggctatacca tgaactgggt caaacaggct      120

ccaggacagg gactggagtg gatcgggctg attaatcctt acaacaacat caccaactac      180

aaccagaagt tcatgggaaa agcaaccttt acagtggaca agagcatttc cacagcctac      240

atggaactga gccggctgac ttcagacgat agcggggtct atttttgtgc aaggctggat      300

tatcgctctt actgggggca gggaactctg gtcactgtct ccgct                      345


<210>  8
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region of 4G10H1L1

<400>  8

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


Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 
            20                  25                  30          


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


Gly Leu Ile Asn Pro Tyr Asn Asn Ile Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


Met Glu Leu Ser Arg Leu Thr Ser Asp Asp Ser Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  9
<211>  327
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized light chain variable region of 4G10H1L1

<400>  9
caggctgtcg tcactcagga accttcactg actgtgagcc caggaggaac tgtcaccctg       60

acatgcggaa gctccaccgg agcagtgacc acatccaact tcgccaattg ggtccaggaa      120

aagccaggcc aggcatttcg atccctgatc ggaggcacaa acaatcgggc ttcttgggtg      180

cccgcaagat tctcaggaag cctgctgggg ggaaaagccg ctctgaccat tagtggcgct      240

cagcctgagg acgaagccga gtacttctgc gctctgtggt atagcaacca ctgggtgttt      300

ggcgggggaa caaagctgac tgtgctg                                          327


<210>  10
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized light chain variable region of 4G10H1L1

<400>  10

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


Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
            20                  25                  30          


Asn Phe Ala Asn Trp Val Gln Glu Lys Pro Gly Gln Ala Phe Arg Ser 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Asn Arg Ala Ser Trp Val Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
65                  70                  75                  80  


Gln Pro Glu Asp Glu Ala Glu Tyr Phe Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  11
<211>  345
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region of 4G10H3L3

<400>  11
caggtgcagc tggtcgagtc tggggccgaa gtgaagaaac ccggcgcctc agtgaaggtc       60

agctgcaagg ccagcgggta cagtttcact ggatatacca tgaactgggt ccgacaggcc      120

cctggccagg ggctggagtg gatcggcctg attaaccctt acaacaacat cactaactac      180

gcacagaagt tccaggggag agtgaccttt acagtggaca ccagcatttc cacagcctac      240

atggaactgt cccggctgag atctgacgat acaggcgtgt acttctgcgc taggctggat      300

taccgcagct attggggaca gggcacactg gtgactgtca gcgca                      345


<210>  12
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region of 4G10H3L3

<400>  12

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


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


Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Leu Ile Asn Pro Tyr Asn Asn Ile Thr Asn Tyr Ala Gln Lys Phe 
    50                  55                  60                  


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


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  13
<211>  327
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized light chain variable region of 4G10H3L3

<400>  13
caggctgtcg tcactcagga accttcactg accgtgtctc ctggcgggac tgtcaccctg       60

acatgcggca gctccacagg ggccgtgacc acaagtaact tcccaaattg ggtccagcag      120

aagccaggac aggctccccg gagtctgatc ggaggcacca acaacaaggc cagctggaca      180

cccgcacggt tcagcggcag cctgctgggc ggcaaggccg ctctgacaat tagcggagcc      240

cagcctgagg acgaagccga gtactattgc gctctgtggt actccaacca ctgggtgttc      300

ggcggcggca ccaagctgac tgtgctg                                          327


<210>  14
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized light chain variable region of 4G10H3L3

<400>  14

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


Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
            20                  25                  30          


Asn Phe Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Ser 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Asn Lys Ala Ser Trp Thr Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
65                  70                  75                  80  


Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  15
<211>  345
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region 4G10H4

<400>  15
caggtgcagc tggtcgagtc tggggccgaa gtgaagaaac ccggcgcctc agtgaaggtc       60

agctgcaagg ccagcgggta cagtttcact ggatatacca tgaactgggt ccgacaggcc      120

cctggccagg ggctggagtg gatcggcctg attaaccctt acaacgacat cactaactac      180

gcacagaagt tccaggggag agtgaccttt acagtggaca ccagcatttc cacagcctac      240

atggaactgt cccggctgag atctgacgat acaggcgtgt acttctgcgc taggctggat      300

taccgcagct attggggaca gggcacactg gtgactgtca gcgca                      345


<210>  16
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region 4G10H4

<400>  16

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


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


Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Leu Ile Asn Pro Tyr Asn Asp Ile Thr Asn Tyr Ala Gln Lys Phe 
    50                  55                  60                  


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


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  17
<211>  345
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region 4G10H5

<400>  17
caggtgcagc tggtcgagtc tggggccgaa gtgaagaaac ccggcgcctc agtgaaggtc       60

agctgcaagg ccagcgggta cagtttcact ggatatacca tgaactgggt ccgacaggcc      120

cctggccagg ggctggagtg gatcggcctg attaaccctt acaacaacat cgataactac      180

gcacagaagt tccaggggag agtgaccttt acagtggaca ccagcatttc cacagcctac      240

atggaactgt cccggctgag atctgacgat acaggcgtgt acttctgcgc taggctggat      300

taccgcagct attggggaca gggcacactg gtgactgtca gcgca                      345


<210>  18
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain variable region 4G10H5

<400>  18

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


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


Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Leu Ile Asn Pro Tyr Asn Asn Ile Asp Asn Tyr Ala Gln Lys Phe 
    50                  55                  60                  


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


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  19
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 4G10 variable heavy chain region consensus sequence


<220>
<221>  X
<222>  (11)..(11)
<223>  Val or Leu

<220>
<221>  X
<222>  (18)..(18)
<223>  Val or Met

<220>
<221>  X
<222>  (20)..(20)
<223>  Val or Ile

<220>
<221>  X
<222>  (34)..(34)
<223>  Met or Val or Leu or Ile or Gly or Ala or Ser or Thr

<220>
<221>  X
<222>  (38)..(38)
<223>  Arg or Lys

<220>
<221>  X
<222>  (56)..(56)
<223>  Asn or Asp or Glu

<220>
<221>  X
<222>  (58)..(58)
<223>  Thr or Asp or Glu or Gly or Ala

<220>
<221>  X
<222>  (61)..(61)
<223>  Ala or Asn

<220>
<221>  X
<222>  (65)..(65)
<223>  Gln or Met

<220>
<221>  X
<222>  (67)..(67)
<223>  Arg or Lys

<220>
<221>  X
<222>  (68)..(68)
<223>  Val or Ala

<220>
<221>  X
<222>  (74)..(74)
<223>  Thr or Lys

<220>
<221>  X
<222>  (87)..(87)
<223>  Arg or Thr

<220>
<221>  X
<222>  (91)..(91)
<223>  Thr or Ser

<400>  19

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


Ser Xaa Lys Xaa Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr 
            20                  25                  30          


Thr Xaa Asn Trp Val Xaa Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Leu Ile Asn Pro Tyr Asn Xaa Ile Xaa Asn Tyr Xaa Gln Lys Phe 
    50                  55                  60                  


Xaa Gly Xaa Xaa Thr Phe Thr Val Asp Xaa Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Xaa Ser Asp Asp Xaa Gly Val Tyr Phe Cys 
                85                  90                  95      


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


Val Ser Ala 
        115 


<210>  20
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 4G10 variable light chain region consensus sequence


<220>
<221>  X
<222>  (35)..(35)
<223>  Pro or Ala

<220>
<221>  X
<222>  (40)..(40)
<223>  Gln or Glu

<220>
<221>  X
<222>  (46)..(46)
<223>  Pro or Phe

<220>
<221>  X
<222>  (56)..(56)
<223>  Lys or Arg or any other amino acid except Met or Cys

<220>
<221>  X
<222>  (58)..(58)
<223>  Ser or Pro

<220>
<221>  X
<222>  (60)..(60)
<223>  Thr or Val

<220>
<221>  X
<222>  (89)..(89)
<223>  Tyr or Phe

<220>
<221>  X
<222>  (93)..(93)
<223>  Trp or any amino acid except Met or Cys

<220>
<221>  X
<222>  (98)..(98)
<223>  Trp or any amino acid except Met or Cys

<400>  20

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


Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 
            20                  25                  30          


Asn Phe Xaa Asn Trp Val Gln Xaa Lys Pro Gly Gln Ala Xaa Arg Ser 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Asn Xaa Ala Xaa Trp Xaa Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 
65                  70                  75                  80  


Gln Pro Glu Asp Glu Ala Glu Tyr Xaa Cys Ala Leu Xaa Tyr Ser Asn 
                85                  90                  95      


His Xaa Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  21
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR1 consensus


<220>
<221>  X
<222>  (4)..(4)
<223>  Met or Val or Leu or Ile or Gly or Ala or Ser or Thr

<400>  21

Gly Tyr Thr Xaa Asn 
1               5   


<210>  22
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR2 consensus sequence


<220>
<221>  X
<222>  (7)..(7)
<223>  Asn or Asp

<220>
<221>  X
<222>  (9)..(9)
<223>  Thr or Asp or Glu or Gly or Ala

<220>
<221>  X
<222>  (12)..(12)
<223>  Ala or Asn

<220>
<221>  X
<222>  (16)..(16)
<223>  Gln or Met

<400>  22

Leu Ile Asn Pro Tyr Asn Xaa Ile Xaa Asn Tyr Xaa Gln Lys Phe Xaa 
1               5                   10                  15      


Gly 
    


<210>  23
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR3 sequence

<400>  23

Leu Asp Tyr Arg Ser Tyr 
1               5       


<210>  24
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR1 consensus sequence


<220>
<221>  X
<222>  (13)..(13)
<223>  Pro or Ala

<400>  24

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Phe Xaa Asn 
1               5                   10                  


<210>  25
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR2 consensus sequence


<220>
<221>  X
<222>  (5)..(5)
<223>  Lys or Arg or any amino acid except Met or Cys

<220>
<221>  X
<222>  (7)..(7)
<223>  Ser or Pro

<400>  25

Gly Thr Asn Asn Xaa Ala Xaa 
1               5           


<210>  26
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR3 consensus sequence


<220>
<221>  X
<222>  (3)..(3)
<223>  Trp or any amino acid except Met or Cys

<220>
<221>  X
<222>  (8)..(8)
<223>  Trp or any amino acid except Met or Cys

<400>  26

Ala Leu Xaa Tyr Ser Asn His Xaa 
1               5               


<210>  27
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR1 sequence

<400>  27

Gly Tyr Ser Phe Thr Gly Tyr Thr 
1               5               


<210>  28
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR2


<220>
<221>  X
<222>  (6)..(6)
<223>  Asn or Asp or Glu

<220>
<221>  X
<222>  (8)..(8)
<223>  Thr or Asp or Glu or Gly or Ala

<400>  28

Ile Asn Pro Tyr Asn Xaa Ile Xaa 
1               5               


<210>  29
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 HCDR3

<400>  29

Ala Arg Leu Asp Tyr Arg Ser Tyr 
1               5               


<210>  30
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR1

<400>  30

Thr Gly Ala Val Thr Thr Ser Asn Phe 
1               5                   


<210>  31
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR2

<400>  31

Gly Thr Asn 
1           


<210>  32
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  4G10 LCDR3


<220>
<221>  X
<222>  (3)..(3)
<223>  Trp or any amino acid except Met or Cys

<220>
<221>  X
<222>  (8)..(8)
<223>  Trp or any amino acid except Met or Cys

<400>  32

Ala Leu Xaa Tyr Ser Asn His Xaa Val 
1               5                   


<210>  33
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary heavy chain IgG1 constant domain

<400>  33

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


Ser Thr Ser Gly Gly 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 Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  34
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary human kappa chain constant domain

<400>  34

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>  35
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  10D1 heavy chain

<400>  35

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


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


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


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


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


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


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


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


Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 


Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 


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


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


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


Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His 
    210                 215                 220                 


Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Pro Ser Val Phe 
225                 230                 235                 240 


Leu Phe Pro Pro Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
                245                 250                 255     


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
            260                 265                 270         


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
        275                 280                 285             


Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
    290                 295                 300                 


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
305                 310                 315                 320 


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


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


Arg Asp Glu Leu Thr Lys Asn Gln Val Leu Thr Cys Leu Val Lys Gly 
        355                 360                 365             


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


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


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


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440             


<210>  36
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  10D1 Light chain

<400>  36

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


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


Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 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                 


