                         SEQUENCE LISTING

<110>  Bristol-Myers Squibb Company
 
<120>  METHODS OF PRODUCING ANTIBODIES IN YEAST

<130>  11837-WO-PCT

<150>  US 61/787,190
<151>  2013-03-15

<150>  US 61/787,029
<151>  2013-03-15

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  212
<212>  PRT
<213>  Homo sapiens

<400>  1

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


Gly Leu Leu Leu Val Leu Pro Ala Ala Phe Pro Ala Pro Val Pro Pro 
            20                  25                  30          


Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr 
        35                  40                  45              


Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile 
    50                  55                  60                  


Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser 
65                  70                  75                  80  


Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala 
                85                  90                  95      


Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu 
            100                 105                 110         


Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr 
        115                 120                 125             


Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln 
    130                 135                 140                 


Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn 
145                 150                 155                 160 


Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu 
                165                 170                 175     


Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His 
            180                 185                 190         


Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala 
        195                 200                 205             


Leu Arg Gln Met 
    210         


<210>  2
<211>  648
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized antibody light chain


<220>
<221>  CDS
<222>  (1)..(648)

<400>  2
gct atc cag atg acc cag tct cct tcc tcc ctg tct gca tct gta gga         48
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly           
1               5                   10                  15                

gac aga gtc acc atc act tgc cag gcc agt cag agc att aac aat gag         96
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu           
            20                  25                  30                    

tta tcc tgg tat cag cag aaa cca ggg aaa gcc cct aag ctc ctg atc        144
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile           
        35                  40                  45                        

tat agg gca tcc act ctg gca tct ggg gtc cca tca agg ttc agc ggc        192
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly           
    50                  55                  60                            

agt gga tct ggg aca gac ttc act ctc acc atc agc agc ctg cag cct        240
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro           
65                  70                  75                  80            

gat gat ttt gca act tat tac tgc caa cag ggt tat agt ctg agg aac        288
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn           
                85                  90                  95                

att gat aat gct ttc ggc gga ggg acc aag gtg gaa atc aaa cgt gtg        336
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Val           
            100                 105                 110                   

gct gca cca tct gtc ttc atc ttc ccg cca tct gat gag cag ttg aaa        384
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys           
        115                 120                 125                       

tct gga act gcc tct gtt gtg tgc ctg ctg aat aac ttc tat ccc aga        432
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg           
    130                 135                 140                           

gag gcc aaa gta cag tgg aag gtg gat aac gcc ctc caa tcg ggt aac        480
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn           
145                 150                 155                 160           

tcc cag gag agt gtc aca gag cag gac agc aag gac agc acc tac agc        528
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser           
                165                 170                 175               

ctc agc agc acc ctg acg ctg agc aaa gca gac tac gag aaa cac aaa        576
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys           
            180                 185                 190                   

gtc tac gcc tgc gaa gtc acc cat cag ggc ctg agc tcg ccc gtc aca        624
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr           
        195                 200                 205                       

aag agc ttc aac agg gga gag tgt                                        648
Lys Ser Phe Asn Arg Gly Glu Cys                                           
    210                 215                                               


<210>  3
<211>  216
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  3

Ala 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 Gln Ala Ser Gln Ser Ile Asn Asn Glu 
            20                  25                  30          


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


Tyr Arg Ala Ser Thr Leu Ala 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  


Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn 
                85                  90                  95      


Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Val 
            100                 105                 110         


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


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


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


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


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


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


Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215     


<210>  4
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized Antibody Light Chain Variable Domain


<220>
<221>  CDS
<222>  (1)..(333)

<220>
<221>  misc_feature
<222>  (24)..(34)
<223>  Light Chain Variable Domain CDR1

<220>
<221>  misc_feature
<222>  (50)..(56)
<223>  Light Chain Variable Domain CDR2

<220>
<221>  misc_feature
<222>  (89)..(100)
<223>  Light Chain Variable Domain CDR3

<400>  4
gct atc cag atg acc cag tct cct tcc tcc ctg tct gca tct gta gga         48
Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly           
1               5                   10                  15                

gac aga gtc acc atc act tgc cag gcc agt cag agc att aac aat gag         96
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu           
            20                  25                  30                    

tta tcc tgg tat cag cag aaa cca ggg aaa gcc cct aag ctc ctg atc        144
Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile           
        35                  40                  45                        

tat agg gca tcc act ctg gca tct ggg gtc cca tca agg ttc agc ggc        192
Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly           
    50                  55                  60                            

agt gga tct ggg aca gac ttc act ctc acc atc agc agc ctg cag cct        240
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro           
65                  70                  75                  80            

gat gat ttt gca act tat tac tgc caa cag ggt tat agt ctg agg aac        288
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn           
                85                  90                  95                

att gat aat gct ttc ggc gga ggg acc aag gtg gaa atc aaa cgt            333
Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg               
            100                 105                 110                   


<210>  5
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  5

Ala 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 Gln Ala Ser Gln Ser Ile Asn Asn Glu 
            20                  25                  30          


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


Tyr Arg Ala Ser Thr Leu Ala 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  


Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn 
                85                  90                  95      


Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105                 110     


<210>  6
<211>  11
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  6

Gln Ala Ser Gln Ser Ile Asn Asn Glu Leu Ser 
1               5                   10      


<210>  7
<211>  7
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  7

Arg Ala Ser Thr Leu Ala Ser 
1               5           


<210>  8
<211>  12
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  8

Gln Gln Gly Tyr Ser Leu Arg Asn Ile Asp Asn Ala 
1               5                   10          


<210>  9
<211>  315
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(315)

<400>  9
gtg gct gca cca tct gtc ttc atc ttc ccg cca tct gat gag cag ttg         48
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu           
1               5                   10                  15                

aaa tct gga act gcc tct gtt gtg tgc ctg ctg aat aac ttc tat ccc         96
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro           
            20                  25                  30                    

aga gag gcc aaa gta cag tgg aag gtg gat aac gcc ctc caa tcg ggt        144
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly           
        35                  40                  45                        

aac tcc cag gag agt gtc aca gag cag gac agc aag gac agc acc tac        192
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr           
    50                  55                  60                            

agc ctc agc agc acc ctg acg ctg agc aaa gca gac tac gag aaa cac        240
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His           
65                  70                  75                  80            

aaa gtc tac gcc tgc gaa gtc acc cat cag ggc ctg agc tcg ccc gtc        288
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val           
                85                  90                  95                

aca aag agc ttc aac agg gga gag tgt                                    315
Thr Lys Ser Phe Asn Arg Gly Glu Cys                                       
            100                 105                                       


<210>  10
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  10

Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 
1               5                   10                  15      


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


Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
        35                  40                  45              


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


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


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


Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105 


<210>  11
<211>  1350
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized Antibody Heavy Chain


<220>
<221>  CDS
<222>  (1)..(1350)

<400>  11
gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct ggg ggg         48
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly           
1               5                   10                  15                

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc tcc ctc agt aac tac         96
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr           
            20                  25                  30                    

tac gtg acc tgg gtc cgt cag gct cca ggg aag ggg ctg gag tgg gtc        144
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val           
        35                  40                  45                        

ggc atc atc tat ggt agt gat gaa acc gcc tac gct acc tcc gct ata        192
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile           
    50                  55                  60                            

ggc cga ttc acc atc tcc aga gac aat tcc aag aac acc ctg tat ctt        240
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu           
65                  70                  75                  80            

caa atg aac agc ctg aga gct gag gac act gct gtg tat tac tgt gct        288
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala           
                85                  90                  95                

aga gat gat agt agt gac tgg gat gca aag ttc aac ttg tgg ggc caa        336
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln           
            100                 105                 110                   

ggg acc ctc gtc acc gtc tcg agc gcc tcc acc aag ggc cca tcg gtc        384
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val           
        115                 120                 125                       

ttc ccc ctg gca ccc tcc tcc aag agc acc tct ggg ggc aca gcg gcc        432
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala           
    130                 135                 140                           

ctg ggc tgc ctg gtc aag gac tac ttc ccc gaa ccg gtg acg gtg tcg        480
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser           
145                 150                 155                 160           

tgg aac tca ggc gcc ctg acc agc ggc gtg cac acc ttc ccg gct gtc        528
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val           
                165                 170                 175               

cta cag tcc tca gga ctc tac tcc ctc agc agc gtg gtg acc gtg ccc        576
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro           
            180                 185                 190                   

tcc agc agc ttg ggc acc cag acc tac atc tgc aac gtg aat cac aag        624
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys           
        195                 200                 205                       

ccc agc aac acc aag gtg gac aag aga gtt gag ccc aaa tct tgt gac        672
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp           
    210                 215                 220                           

aaa act cac aca tgc cca ccg tgc cca gca cct gaa ctc ctg ggg gga        720
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly           
225                 230                 235                 240           

ccg tca gtc ttc ctc ttc ccc cca aaa ccc aag gac acc ctc atg atc        768
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile           
                245                 250                 255               

tcc cgg acc cct gag gtc aca tgc gtg gtg gtg gac gtg agc cac gaa        816
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu           
            260                 265                 270                   

gac cct gag gtc aag ttc aac tgg tac gtg gac ggc gtg gag gtg cat        864
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His           
        275                 280                 285                       

aat gcc aag aca aag ccg cgg gag gag cag tac gcc agc acg tac cgt        912
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg           
    290                 295                 300                           

gtg gtc agc gtc ctc acc gtc ctg cac cag gac tgg ctg aat ggc aag        960
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys           
305                 310                 315                 320           

gag tac aag tgc aag gtc tcc aac aaa gcc ctc cca gcc ccc atc gag       1008
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu           
                325                 330                 335               

aaa acc atc tcc aaa gcc aaa ggg cag ccc cga gaa cca cag gtg tac       1056
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr           
            340                 345                 350                   

acc ctg ccc cca tcc cgg gag gag atg acc aag aac cag gtc agc ctg       1104
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu           
        355                 360                 365                       

acc tgc ctg gtc aaa ggc ttc tat ccc agc gac atc gcc gtg gag tgg       1152
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp           
    370                 375                 380                           

gag agc aat ggg cag ccg gag aac aac tac aag acc acg cct ccc gtg       1200
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val           
385                 390                 395                 400           

ctg gac tcc gac ggc tcc ttc ttc ctc tac agc aag ctc acc gtg gac       1248
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp           
                405                 410                 415               

aag agc agg tgg cag cag ggg aac gtc ttc tca tgc tcc gtg atg cat       1296
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His           
            420                 425                 430                   

gag gct ctg cac aac cac tac acg cag aag agc ctc tcc ctg tct ccg       1344
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro           
        435                 440                 445                       

ggt aaa                                                               1350
Gly Lys                                                                   
    450                                                                   


<210>  12
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  12

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 Ser Leu Ser Asn Tyr 
            20                  25                  30          


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


Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile 
    50                  55                  60                  


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


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


Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  13
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized Antibody Heavy Chain Variable Domain


<220>
<221>  CDS
<222>  (1)..(360)

<220>
<221>  misc_feature
<222>  (31)..(35)
<223>  Heavy Chain Variable Domain CDR1

<220>
<221>  misc_feature
<222>  (50)..(65)
<223>  Heavy Chain Variable Domain CDR2

<220>
<221>  misc_feature
<222>  (98)..(109)
<223>  Heavy Chain Variable Domain CDR3

<400>  13
gag gtg cag ctg gtg gag tct ggg gga ggc ttg gtc cag cct ggg ggg         48
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly           
1               5                   10                  15                

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc tcc ctc agt aac tac         96
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr           
            20                  25                  30                    

tac gtg acc tgg gtc cgt cag gct cca ggg aag ggg ctg gag tgg gtc        144
Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val           
        35                  40                  45                        

ggc atc atc tat ggt agt gat gaa acc gcc tac gct acc tcc gct ata        192
Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile           
    50                  55                  60                            

ggc cga ttc acc atc tcc aga gac aat tcc aag aac acc ctg tat ctt        240
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu           
65                  70                  75                  80            

caa atg aac agc ctg aga gct gag gac act gct gtg tat tac tgt gct        288
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala           
                85                  90                  95                

aga gat gat agt agt gac tgg gat gca aag ttc aac ttg tgg ggc caa        336
Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln           
            100                 105                 110                   

ggg acc ctc gtc acc gtc tcg agc                                        360
Gly Thr Leu Val Thr Val Ser Ser                                           
        115                 120                                           


<210>  14
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  14

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 Ser Leu Ser Asn Tyr 
            20                  25                  30          


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


Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile 
    50                  55                  60                  


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


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


Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  15
<211>  5
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  15

Asn Tyr Tyr Val Thr 
1               5   


<210>  16
<211>  16
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  16

Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile Gly 
1               5                   10                  15      


<210>  17
<211>  12
<212>  PRT
<213>  Oryctolagus cuniculus

<400>  17

Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu 
1               5                   10          


<210>  18
<211>  990
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(990)

<400>  18
gcc tcc acc aag ggc cca tcg gtc ttc ccc ctg gca ccc tcc tcc aag         48
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys           
1               5                   10                  15                

agc acc tct ggg ggc aca gcg gcc ctg ggc tgc ctg gtc aag gac tac         96
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr           
            20                  25                  30                    

ttc ccc gaa ccg gtg acg gtg tcg tgg aac tca ggc gcc ctg acc agc        144
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser           
        35                  40                  45                        

ggc gtg cac acc ttc ccg gct gtc cta cag tcc tca gga ctc tac tcc        192
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser           
    50                  55                  60                            

ctc agc agc gtg gtg acc gtg ccc tcc agc agc ttg ggc acc cag acc        240
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr           
65                  70                  75                  80            

tac atc tgc aac gtg aat cac aag ccc agc aac acc aag gtg gac aag        288
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys           
                85                  90                  95                

aga gtt gag ccc aaa tct tgt gac aaa act cac aca tgc cca ccg tgc        336
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys           
            100                 105                 110                   

cca gca cct gaa ctc ctg ggg gga ccg tca gtc ttc ctc ttc ccc cca        384
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro           
        115                 120                 125                       

aaa ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca tgc        432
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys           
    130                 135                 140                           

gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac tgg        480
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp           
145                 150                 155                 160           

tac gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag        528
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu           
                165                 170                 175               

gag cag tac gcc agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg        576
Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu           
            180                 185                 190                   

cac cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc aac        624
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn           
        195                 200                 205                       

aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa ggg        672
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly           
    210                 215                 220                           

cag ccc cga gaa cca cag gtg tac acc ctg ccc cca tcc cgg gag gag        720
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu           
225                 230                 235                 240           

atg acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tat        768
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr           
                245                 250                 255               

ccc agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac        816
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn           
            260                 265                 270                   

aac tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc        864
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe           
        275                 280                 285                       

ctc tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg aac        912
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn           
    290                 295                 300                           

gtc ttc tca tgc tcc gtg atg cat gag gct ctg cac aac cac tac acg        960
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr           
305                 310                 315                 320           

cag aag agc ctc tcc ctg tct ccg ggt aaa                                990
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys                                   
                325                 330                                   


<210>  19
<211>  330
<212>  PRT
<213>  Homo sapiens

<400>  19

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      


Arg 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 Ala 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 Glu Glu 
225                 230                 235                 240 


Met 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>  20
<211>  483
<212>  DNA
<213>  Pichia pastoris


<220>
<221>  misc_feature
<222>  (1)..(483)
<223>  Glyceraldehyde-3-Phosphate dehydrogenase (GAP) promoter

<400>  20
agatcttttt tgtagaaatg tcttggtgtc ctcgtccaat caggtagcca tctctgaaat       60

atctggctcc gttgcaactc cgaacgacct gctggcaacg taaaattctc cggggtaaaa      120

cttaaatgtg gagtaatgga accagaaacg tctcttccct tctctctcct tccaccgccc      180

gttaccgtcc ctaggaaatt ttactctgct ggagagcttc ttctacggcc cccttgcagc      240

aatgctcttc ccagcattac gttgcgggta aaacggaggt cgtgtacccg acctagcagc      300

ccagggatgg aaaagtcccg gccgtcgctg gcaataatag cgggcggacg catgtcatga      360

gattattgga aaccaccaga atcgaatata aaaggcgaac acctttccca attttggttt      420

ctcctgaccc aaagacttta aatttaattt atttgtccct atttcaatca attgaacaac      480

tat                                                                    483


