               SEQUENCE LISTING

<110> Merck Patent GmbH

<120> ANTI-CEACAM5 ANTIBODIES AND CONJUGATES AND USES THEREOF

<130> P20-166 WO-PCT

<150> EP20195559.8
<151> 2020-09-10
<150> EP20194711.6
<151> 2020-09-04

<160> 30

<170> BiSSAP 1.3.6

<210> 1
<211> 702
<212> PRT
<213> Homo sapiens


<220> 
<223> Human CEACAM5 protein sequence according to GenBank accession number AAA51967.1

<400> 1
Met Glu Ser Pro Ser Ala Pro Pro His Arg Trp Cys Ile Pro Trp Gln 
1               5                   10                  15      
Arg Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr 
            20                  25                  30          
Thr Ala Lys Leu Thr Ile Glu Ser Thr Pro Phe Asn Val Ala Glu Gly 
        35                  40                  45              
Lys Glu Val Leu Leu Leu Val His Asn Leu Pro Gln His Leu Phe Gly 
    50                  55                  60                  
Tyr Ser Trp Tyr Lys Gly Glu Arg Val Asp Gly Asn Arg Gln Ile Ile 
65                  70                  75                  80  
Gly Tyr Val Ile Gly Thr Gln Gln Ala Thr Pro Gly Pro Ala Tyr Ser 
                85                  90                  95      
Gly Arg Glu Ile Ile Tyr Pro Asn Ala Ser Leu Leu Ile Gln Asn Ile 
            100                 105                 110         
Ile Gln Asn Asp Thr Gly Phe Tyr Thr Leu His Val Ile Lys Ser Asp 
        115                 120                 125             
Leu Val Asn Glu Glu Ala Thr Gly Gln Phe Arg Val Tyr Pro Glu Leu 
    130                 135                 140                 
Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Lys Pro Val Glu Asp Lys 
145                 150                 155                 160 
Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Thr Gln Asp Ala Thr Tyr 
                165                 170                 175     
Leu Trp Trp Val Asn Asn Gln Ser Leu Pro Val Ser Pro Arg Leu Gln 
            180                 185                 190         
Leu Ser Asn Gly Asn Arg Thr Leu Thr Leu Phe Asn Val Thr Arg Asn 
        195                 200                 205             
Asp Thr Ala Ser Tyr Lys Cys Glu Thr Gln Asn Pro Val Ser Ala Arg 
    210                 215                 220                 
Arg Ser Asp Ser Val Ile Leu Asn Val Leu Tyr Gly Pro Asp Ala Pro 
225                 230                 235                 240 
Thr Ile Ser Pro Leu Asn Thr Ser Tyr Arg Ser Gly Glu Asn Leu Asn 
                245                 250                 255     
Leu Ser Cys His Ala Ala Ser Asn Pro Pro Ala Gln Tyr Ser Trp Phe 
            260                 265                 270         
Val Asn Gly Thr Phe Gln Gln Ser Thr Gln Glu Leu Phe Ile Pro Asn 
        275                 280                 285             
Ile Thr Val Asn Asn Ser Gly Ser Tyr Thr Cys Gln Ala His Asn Ser 
    290                 295                 300                 
Asp Thr Gly Leu Asn Arg Thr Thr Val Thr Thr Ile Thr Val Tyr Ala 
305                 310                 315                 320 
Glu Pro Pro Lys Pro Phe Ile Thr Ser Asn Asn Ser Asn Pro Val Glu 
                325                 330                 335     
Asp Glu Asp Ala Val Ala Leu Thr Cys Glu Pro Glu Ile Gln Asn Thr 
            340                 345                 350         
Thr Tyr Leu Trp Trp Val Asn Asn Gln Ser Leu Pro Val Ser Pro Arg 
        355                 360                 365             
Leu Gln Leu Ser Asn Asp Asn Arg Thr Leu Thr Leu Leu Ser Val Thr 
    370                 375                 380                 
Arg Asn Asp Val Gly Pro Tyr Glu Cys Gly Ile Gln Asn Glu Leu Ser 
385                 390                 395                 400 
Val Asp His Ser Asp Pro Val Ile Leu Asn Val Leu Tyr Gly Pro Asp 
                405                 410                 415     
Asp Pro Thr Ile Ser Pro Ser Tyr Thr Tyr Tyr Arg Pro Gly Val Asn 
            420                 425                 430         
Leu Ser Leu Ser Cys His Ala Ala Ser Asn Pro Pro Ala Gln Tyr Ser 
        435                 440                 445             
Trp Leu Ile Asp Gly Asn Ile Gln Gln His Thr Gln Glu Leu Phe Ile 
    450                 455                 460                 
Ser Asn Ile Thr Glu Lys Asn Ser Gly Leu Tyr Thr Cys Gln Ala Asn 
465                 470                 475                 480 
Asn Ser Ala Ser Gly His Ser Arg Thr Thr Val Lys Thr Ile Thr Val 
                485                 490                 495     
Ser Ala Glu Leu Pro Lys Pro Ser Ile Ser Ser Asn Asn Ser Lys Pro 
            500                 505                 510         
Val Glu Asp Lys Asp Ala Val Ala Phe Thr Cys Glu Pro Glu Ala Gln 
        515                 520                 525             
Asn Thr Thr Tyr Leu Trp Trp Val Asn Gly Gln Ser Leu Pro Val Ser 
    530                 535                 540                 
Pro Arg Leu Gln Leu Ser Asn Gly Asn Arg Thr Leu Thr Leu Phe Asn 
545                 550                 555                 560 
Val Thr Arg Asn Asp Ala Arg Ala Tyr Val Cys Gly Ile Gln Asn Ser 
                565                 570                 575     
Val Ser Ala Asn Arg Ser Asp Pro Val Thr Leu Asp Val Leu Tyr Gly 
            580                 585                 590         
Pro Asp Thr Pro Ile Ile Ser Pro Pro Asp Ser Ser Tyr Leu Ser Gly 
        595                 600                 605             
Ala Asn Leu Asn Leu Ser Cys His Ser Ala Ser Asn Pro Ser Pro Gln 
    610                 615                 620                 
Tyr Ser Trp Arg Ile Asn Gly Ile Pro Gln Gln His Thr Gln Val Leu 
625                 630                 635                 640 
Phe Ile Ala Lys Ile Thr Pro Asn Asn Asn Gly Thr Tyr Ala Cys Phe 
                645                 650                 655     
Val Ser Asn Leu Ala Thr Gly Arg Asn Asn Ser Ile Val Lys Ser Ile 
            660                 665                 670         
Thr Val Ser Ala Ser Gly Thr Ser Pro Gly Leu Ser Ala Gly Ala Thr 
        675                 680                 685             
Val Gly Ile Met Ile Gly Val Leu Val Gly Val Ala Leu Ile 
    690                 695                 700         

<210> 2
<211> 705
<212> PRT
<213> Macaca fascicularis


<220> 
<223> Macaca fascicularis CEACAM5 protein sequence (NCBI Reference Sequence XP_005589491.1)

<400> 2
Met Gly Ser Pro Ser Ala Pro Leu His Arg Trp Cys Ile Pro Trp Gln 
1               5                   10                  15      
Thr Leu Leu Leu Thr Ala Ser Leu Leu Thr Phe Trp Asn Pro Pro Thr 
            20                  25                  30          
Thr Ala Gln Leu Thr Ile Glu Ser Arg Pro Phe Asn Val Ala Glu Gly 
        35                  40                  45              
Lys Glu Val Leu Leu Leu Ala His Asn Val Ser Gln Asn Leu Phe Gly 
    50                  55                  60                  
Tyr Ile Trp Tyr Lys Gly Glu Arg Val Asp Ala Ser Arg Arg Ile Gly 
65                  70                  75                  80  
Ser Cys Val Ile Arg Thr Gln Gln Ile Thr Pro Gly Pro Ala His Ser 
                85                  90                  95      
Gly Arg Glu Thr Ile Asp Phe Asn Ala Ser Leu Leu Ile His Asn Val 
            100                 105                 110         
Thr Gln Ser Asp Thr Gly Ser Tyr Thr Ile Gln Val Ile Lys Glu Asp 
        115                 120                 125             
Leu Val Asn Glu Glu Ala Thr Gly Gln Phe Arg Val Tyr Pro Glu Leu 
    130                 135                 140                 
Pro Lys Pro Tyr Ile Ser Ser Asn Asn Ser Asn Pro Val Glu Asp Lys 
145                 150                 155                 160 
Asp Ala Val Ala Leu Thr Cys Glu Pro Glu Thr Gln Asp Thr Thr Tyr 
                165                 170                 175     
Leu Trp Trp Val Asn Asn Gln Ser Leu Pro Val Ser Pro Arg Leu Glu 
            180                 185                 190         
Leu Ser Ser Asp Asn Arg Thr Leu Thr Val Phe Asn Ile Pro Arg Asn 
        195                 200                 205             
Asp Thr Thr Ser Tyr Lys Cys Glu Thr Gln Asn Pro Val Ser Val Arg 
    210                 215                 220                 
Arg Ser Asp Pro Val Thr Leu Asn Val Leu Tyr Gly Pro Asp Ala Pro 
225                 230                 235                 240 
Thr Ile Ser Pro Leu Asn Thr Pro Tyr Arg Ala Gly Glu Asn Leu Asn 
                245                 250                 255     
Leu Ser Cys His Ala Ala Ser Asn Pro Thr Ala Gln Tyr Phe Trp Phe 
            260                 265                 270         
Val Asn Gly Thr Phe Gln Gln Ser Thr Gln Glu Leu Phe Ile Pro Asn 
        275                 280                 285             
Ile Thr Val Asn Asn Ser Gly Ser Tyr Met Cys Gln Ala His Asn Ser 
    290                 295                 300                 
Ala Thr Gly Leu Asn Arg Thr Thr Val Thr Ala Ile Thr Val Tyr Ala 
305                 310                 315                 320 
Glu Leu Pro Lys Pro Tyr Ile Thr Ser Asn Asn Ser Asn Pro Ile Glu 
                325                 330                 335     
Asp Lys Asp Ala Val Thr Leu Thr Cys Glu Pro Glu Thr Gln Asp Thr 
            340                 345                 350         
Thr Tyr Leu Trp Trp Val Asn Asn Gln Ser Leu Ser Val Ser Ser Arg 
        355                 360                 365             
Leu Glu Leu Ser Asn Asp Asn Arg Thr Leu Thr Val Phe Asn Ile Pro 
    370                 375                 380                 
Arg Asn Asp Thr Thr Phe Tyr Glu Cys Glu Thr Gln Asn Pro Val Ser 
385                 390                 395                 400 
Val Arg Arg Ser Asp Pro Val Thr Leu Asn Val Leu Tyr Gly Pro Asp 
                405                 410                 415     
Ala Pro Thr Ile Ser Pro Leu Asn Thr Pro Tyr Arg Ala Gly Glu Asn 
            420                 425                 430         
Leu Asn Leu Ser Cys His Ala Ala Ser Asn Pro Ala Ala Gln Tyr Ser 
        435                 440                 445             
Trp Phe Val Asn Gly Thr Phe Gln Gln Ser Thr Gln Glu Leu Phe Ile 
    450                 455                 460                 
Pro Asn Ile Thr Val Asn Asn Ser Gly Ser Tyr Met Cys Gln Ala His 
465                 470                 475                 480 
Asn Ser Ala Thr Gly Leu Asn Arg Thr Thr Val Thr Ala Ile Thr Val 
                485                 490                 495     
Tyr Val Glu Leu Pro Lys Pro Tyr Ile Ser Ser Asn Asn Ser Asn Pro 
            500                 505                 510         
Ile Glu Asp Lys Asp Ala Val Thr Leu Thr Cys Glu Pro Val Ala Glu 
        515                 520                 525             
Asn Thr Thr Tyr Leu Trp Trp Val Asn Asn Gln Ser Leu Ser Val Ser 
    530                 535                 540                 
Pro Arg Leu Gln Leu Ser Asn Gly Asn Arg Ile Leu Thr Leu Leu Ser 
545                 550                 555                 560 
Val Thr Arg Asn Asp Thr Gly Pro Tyr Glu Cys Gly Ile Gln Asn Ser 
                565                 570                 575     
Glu Ser Ala Lys Arg Ser Asp Pro Val Thr Leu Asn Val Thr Tyr Gly 
            580                 585                 590         
Pro Asp Thr Pro Ile Ile Ser Pro Pro Asp Leu Ser Tyr Arg Ser Gly 
        595                 600                 605             
Ala Asn Leu Asn Leu Ser Cys His Ser Asp Ser Asn Pro Ser Pro Gln 
    610                 615                 620                 
Tyr Ser Trp Leu Ile Asn Gly Thr Leu Arg Gln His Thr Gln Val Leu 
625                 630                 635                 640 
Phe Ile Ser Lys Ile Thr Ser Asn Asn Asn Gly Ala Tyr Ala Cys Phe 
                645                 650                 655     
Val Ser Asn Leu Ala Thr Gly Arg Asn Asn Ser Ile Val Lys Asn Ile 
            660                 665                 670         
Ser Val Ser Ser Gly Asp Ser Ala Pro Gly Ser Ser Gly Leu Ser Ala 
        675                 680                 685             
Arg Ala Thr Val Gly Ile Ile Ile Gly Met Leu Val Gly Val Ala Leu 
    690                 695                 700                 
Met 
705 

<210> 3
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> CDR1-H of mAb1

<400> 3
Asp Gly Ser Val Ser Arg Gly Gly Tyr Tyr 
1               5                   10  

<210> 4
<211> 7
<212> PRT
<213> Artificial Sequence


<220> 
<223> CDR2-H of mAb1

<400> 4
Ile Tyr Tyr Ser Gly Ser Thr 
1               5           

<210> 5
<211> 11
<212> PRT
<213> Artificial Sequence


<220> 
<223> CDR3-H of mAb1

<400> 5
Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr 
1               5                   10      

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


<220> 
<223> CDR1-L of mAb1

<400> 6
Gln Ser Val Arg Ser Asn 
1               5       

<210> 7
<211> 3
<212> PRT
<213> Artificial Sequence


<220> 
<223> CDR2-L of mAb1

<400> 7
Ala Ala Ser
1               

<210> 8
<211> 9
<212> PRT
<213> Artificial Sequence


<220> 
<223> CDR3-L of mAb1

<400> 8
Gln Gln Tyr Thr Asn Trp Pro Phe Thr 
1               5                   

<210> 9
<211> 119
<212> PRT
<213> Artificial Sequence


<220> 
<223> VH of mAb1

<400> 9
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser 
        115                 

<210> 10
<211> 107
<212> PRT
<213> Artificial Sequence


<220> 
<223> VL of mAb1

<400> 10
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys 
            100                 105         

<210> 11
<211> 328
<212> PRT
<213> Artificial Sequence


<220> 
<223> CH of mAb1

<400> 11
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 Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
        115                 120                 125             
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
    130                 135                 140                 
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
145                 150                 155                 160 
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
                165                 170                 175     
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
            180                 185                 190         
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
        195                 200                 205             
Ala Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
    210                 215                 220                 
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
225                 230                 235                 240 
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
                245                 250                 255     
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
            260                 265                 270         
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
        275                 280                 285             
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
    290                 295                 300                 
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
305                 310                 315                 320 
Lys Ser Leu Ser Leu Ser Pro Gly 
                325             

<210> 12
<211> 107
<212> PRT
<213> Artificial Sequence


<220> 
<223> CL of mAb1

<400> 12
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> 13
<211> 447
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of mAb1

<400> 13
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser 
225                 230                 235                 240 
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    290                 295                 300                 
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ser Ser Ile Glu Lys Thr 
                325                 330                 335     
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        355                 360                 365             
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445         

<210> 14
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of mAb1

<400> 14
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 15
<211> 1404
<212> DNA
<213> Artificial Sequence


<220> 
<223> DNA sequence encoding HC of mAb1

<400> 15
atggagaccg acaccctgct gctgtgggtg ctgctgctgt gggtgcccgg gtcgaccggt      60

gaggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcacagac cctgtccctc     120

acctgcactg tctctgatgg ctccgtcagc aggggtggtt actacttgac ctggatccgc     180

cagcacccag ggaagggcct ggagtggatt gggtacatct attacagtgg gagcacctac     240

ttcaacccgt ccctcaggag tcgggttacc atgtcagtag acacgtctaa gaaccagttc     300

tccctgaagc tgagctctgt gactgccgcg gacacggccg tgtattactg tgcgagaggg     360

atagcagtgg ctccctttga ctactggggc cagggaaccc tggtcaccgt ctcttcagct     420

agcaccaagg gccccagcgt gttccccctg gcccccagca gcaagtccac aagcggagga     480

acagccgccc tgggctgcct ggtgaaggac tacttccccg agcccgtgac cgtgtcctgg     540

aacagcggag ccctgacctc cggcgtgcac accttccccg ccgtgctgca gagcagcggc     600

ctgtacagcc tgagcagcgt ggtgacagtg ccaagcagca gcctgggaac ccagacctac     660

atctgcaacg tgaaccacaa gcccagcaac accaaggtgg acaagagagt ggagcccaag     720

agctgcgaca agacccatac ctgtccaccc tgcccagccc ccccagtggc cggaccctcc     780

gtgttcctgt tcccccccaa gcccaaggac accctgatga tcagcaggac ccccgaggtg     840

acctgcgtgg tggtggacgt gagccacgag gacccagagg tgaagttcaa ttggtatgtg     900

gacggcgtgg aggtgcacaa cgccaagacc aagcccagag aggaacagta caacagcacc     960

tacagggtgg tgtccgtgct gaccgtgctg caccaggact ggctgaacgg caaggaatac    1020

aagtgcaagg tctccaacaa ggccctgccc tccagcatcg agaaaaccat cagcaaggcc    1080

aagggccagc cacgggagcc ccaggtgtac acactgcccc catctcggga agaaatgacc    1140

aagaaccagg tgtccctgac ctgtctggtg aagggctttt accccagcga catcgccgtg    1200

gagtgggaga gcaacggcca gcccgagaac aactacaaga ccaccccccc tgtgctggac    1260

agcgacggca gcttcttcct gtacagcaag ctgaccgtgg acaagtccag gtggcagcag    1320

ggcaacgtgt tcagctgcag cgtgatgcac gaggccctgc acaaccacta cacacagaag    1380

agcctgagcc tgtcccccgg ctga                                           1404


<210> 16
<211> 708
<212> DNA
<213> Artificial Sequence


<220> 
<223> DNA sequence encoding LC of mAb1

<400> 16
atgagggccc tgctggctag actgctgctg tgcgtgctgg tcgtgtccga cagcaagggc      60

gaaatcgtac tcacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc     120

ctctcctgca ggaccagtca gagtgttcgc agcaacttag cctggtacca gcagaagcct     180

ggccaggctc ccaggctcct catctatgct gcatccacca gggccactgg tatcccagcc     240

aggttcagtg gcagtgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct     300

gaagattttg cagtttatta ctgtcagcag tatactaact ggccattcac tttcggccct     360

gggaccaaag tggacatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca     420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat     480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag     540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg     600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc     660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttgatag                  708


<210> 17
<211> 449
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of antibody hu8G4

<400> 17
Glu Val Gln Leu Val Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Leu Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    

<210> 18
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of antibody hu8G4

<400> 18
Glu Thr Thr Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Gly Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 19
<211> 449
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of optimized antibody Variant 1

<400> 19
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Leu Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    

<210> 20
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of optimized antibody Variant 1

<400> 20
Glu Thr Thr Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Gly Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 21
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of optimized antibody Variant 2

<400> 21
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 22
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of optimized antibody Variant 4

<400> 22
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 23
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of optimized antibody Variant 5

<400> 23
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 24
<211> 449
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of optimized antibody Variant 6

<400> 24
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    

<210> 25
<211> 450
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of huMab2-3 (allotype)

<400> 25
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Gly Gly 
1               5                   10                  15      
Ser Leu Ser Leu Ser Cys Ala Ala Ser Gly Phe Val Phe Ser Ser Tyr 
            20                  25                  30          
Asp Met Ser Trp Val Arg Gln Thr Pro Glu Arg Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Tyr Ile Ser Ser Gly Gly Gly Ile Thr Tyr Ala Pro Ser Thr Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Ala His Tyr Phe Gly Ser Ser Gly Pro Phe Ala Tyr 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 Asn 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> 26
<211> 214
<212> PRT
<213> Artificial Sequence


<220> 
<223> LC of huMab2-3

<400> 26
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Phe Ser Tyr 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys Leu Leu Val 
        35                  40                  45              
Tyr Asn Thr Arg Thr Leu Ala Glu Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His His Tyr Gly Thr Pro Phe 
                85                  90                  95      
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210> 27
<211> 449
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of hmn-14

<400> 27
Glu 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 Ser Ala Ser Gly Phe Asp Phe Thr Thr Tyr 
            20                  25                  30          
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Glu Ile His Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu 
    50                  55                  60                  
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Phe 
65                  70                  75                  80  
Leu Gln Met Asp Ser Leu Arg Pro Glu Asp Thr Gly Val Tyr Phe Cys 
                85                  90                  95      
Ala Ser Leu Tyr Phe Gly Phe Pro Trp Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Pro Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    

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


<220> 
<223> LC of hmn-14

<400> 28
Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ser 
            20                  25                  30          
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Trp Thr Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Leu Tyr Arg Ser 
                85                  90                  95      
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro 
            100                 105                 110         
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
        115                 120                 125             
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
    130                 135                 140                 
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
145                 150                 155                 160 
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                165                 170                 175     
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
            180                 185                 190         
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
        195                 200                 205             
Asn Arg Gly Glu Cys 
    210             

<210> 29
<211> 441
<212> PRT
<213> Artificial Sequence


<220> 
<223> HC of rb8G4

<400> 29
Glu Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Asp Gly Ser Val Ser Arg Gly 
            20                  25                  30          
Gly Tyr Tyr Leu Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Phe Asn Pro Ser 
    50                  55                  60                  
Leu Arg Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Gly Ile Ala Val Ala Pro Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ser Gln Pro Lys Ala Pro Ser Val Phe Pro 
        115                 120                 125             
Leu Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly 
    130                 135                 140                 
Cys Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn 
145                 150                 155                 160 
Ser Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln 
                165                 170                 175     
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser 
            180                 185                 190         
Ser Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys 
        195                 200                 205             
Val Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Thr Cys Pro 
    210                 215                 220                 
Pro Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys 
225                 230                 235                 240 
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                245                 250                 255     
Val Val Asp Val Ser Glu Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr 
            260                 265                 270         
Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln 
        275                 280                 285             
Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His 
    290                 295                 300                 
Glu Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys 
305                 310                 315                 320 
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln 
                325                 330                 335     
Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu 
            340                 345                 350         
Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro 
        355                 360                 365             
Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn 
    370                 375                 380                 
Tyr Lys Thr Thr Pro Ala Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu 
385                 390                 395                 400 
Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val 
                405                 410                 415     
Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
            420                 425                 430         
Lys Ser Ile Ser Arg Ser Pro Gly Lys 
        435                 440     

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


<220> 
<223> LC of rb8G4

<400> 30
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Thr Asn Trp Pro Phe 
                85                  90                  95      
Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Asp Pro Val Ala 
            100                 105                 110         
Pro Ser Val Leu Leu Phe Pro Pro Ser Lys Glu Glu Leu Thr Thr Gly 
        115                 120                 125             
Thr Ala Thr Ile Val Cys Val Ala Asn Lys Phe Tyr Pro Ser Asp Ile 
    130                 135                 140                 
Thr Val Thr Trp Lys Val Asp Gly Thr Thr Gln Gln Ser Gly Ile Glu 
145                 150                 155                 160 
Asn Ser Lys Thr Pro Gln Ser Pro Glu Asp Asn Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Ser Leu Thr Ser Ala Gln Tyr Asn Ser His Ser Val Tyr 
            180                 185                 190         
Thr Cys Glu Val Val Gln Gly Ser Ala Ser Pro Ile Val Gln Ser Phe 
        195                 200                 205             
Asn Arg Gly Asp Cys 
    210             

