                         SEQUENCE LISTING

<110>  The General Hospital Corporation
 
<120>  Humanized mAb107

<130>  29539-0415WO1

<150>  63/166,711
<151>  2021-03-26

<160>  18    

<170>  PatentIn version 3.5

<210>  1
<211>  122
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized Heavy Chain mAb107

<400>  1

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


Ser Val Lys Val Ser Cys Lys Pro Ser Gly Phe Asn Ile Lys Asp Ile 
            20                  25                  30          


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


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


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


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


Ala Ser Glu Gly His Tyr Gly Tyr Asp Gly Tyr Ala Met Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120         


<210>  2
<211>  113
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized Light Chain mAb107

<400>  2

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Asn Leu Leu Tyr Ser 
            20                  25                  30          


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


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 
                85                  90                  95      


Tyr Tyr Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


Lys 
    


<210>  3
<211>  218
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized Heavy Chain mAb107 IgG4kappa

<400>  3

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


Ser Val Lys Val Ser Cys Lys Pro Ser Gly Phe Asn Ile Lys Asp Ile 
            20                  25                  30          


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


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


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


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


Ala Ser Glu Gly His Tyr Gly Tyr Asp Gly Tyr Ala Met Asp Tyr Trp 
            100                 105                 110         


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


Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 
    130                 135                 140                 


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


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


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


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


Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 
    210                 215             


<210>  4
<211>  220
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized Light Chain mAb107 IgG4kappa

<400>  4

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Asn Leu Leu Tyr Ser 
            20                  25                  30          


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


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 
                85                  90                  95      


Tyr Tyr Ser Tyr Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


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


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


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


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


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


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


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


<210>  5
<211>  6
<212>  PRT
<213>  Artificial

<220>
<223>  CDR1 of the VH of SEQ ID NO: 1

<400>  5

Gly Phe Asn Ile Lys Asp 
1               5       


<210>  6
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  CDR2 of the VH of SEQ ID NO:1

<400>  6

Pro Ala Asp Asp Lys Thr Lys 
1               5           


<210>  7
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  CDR3 of the VH of SEQ ID NO: 1

<400>  7

Gly His Tyr Gly Tyr Asp Gly Tyr Ala 
1               5                   


<210>  8
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  CDR1 of the VL of SEQ ID NO: 2

<400>  8

Ser Gln Asn Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr 
1               5                   10              


<210>  9
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  CDR2 of the VL of SEQ ID NO: 2

<400>  9

Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg 
1               5                   10          


<210>  10
<211>  6
<212>  PRT
<213>  Artificial

<220>
<223>  CDR3 of the VL of SEQ ID NO: 2

<400>  10

Tyr Tyr Ser Tyr Pro Leu 
1               5       


<210>  11
<211>  1413
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized mutagenized mAB 107 IgG4kappa heavy chain V5

<400>  11
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt       60

gaccaggtgc agctggtgca gagcggcgcg gaagtgaaga aaccgggcgc gagcgtgaaa      120

gtgagctgca agccgagcgg ctttaacatt aaagatattt atatgcagtg ggtgaggcag      180

gcgccgggcc agcgcctgga atggattggc cgcattgatc cggcggacga taaaaccaaa      240

tatgatccga aatttcaggg ccgcgcgacc attaccgcgg ataccagcgc gagcaccgcg      300

tatctggaac tgagcagcct gcgcagcgaa gataccgcgg tgtattattg cgcgagcgaa      360

ggccattatg gctatgatgg ctatgcgatg gattattggg gccagggcac caccgtgacc      420

gtgagcagcg ctagcaccaa gggcccatcc gtcttccccc tggcgccctg ctccaggagc      480

acctccgaga gcacagccgc cctgggctgc ctggtcaagg actacttccc cgaaccggtg      540

acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta      600

cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc      660

acgaagacct acacctgcaa cgtagatcac aagcccagca acaccaaggt ggacaagaga      720

gttgagtcca aatatggtcc cccatgccca ccatgcccag cacctgagtt cctgggggga      780

ccatcagtct tcctgttccc cccaaaaccc aaggacactc tcatgatctc ccggacccct      840

gaggtcacgt gcgtggtggt ggacgtgagc caggaagacc ccgaggtcca gttcaactgg      900

tacgtggatg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagttcaac      960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaacggcaag     1020

gagtacaagt gcaaggtctc caacaaaggc ctcccgtcct ccatcgagaa aaccatctcc     1080

aaagccaaag ggcagccccg agagccacag gtgtacaccc tgcccccatc ccaggaggag     1140

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctaccc cagcgacatc     1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1260

ctggactccg acggctcctt cttcctctac agcaggctaa ccgtggacaa gagcaggtgg     1320

caggagggga atgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacaca     1380

cagaagagcc tctccctgtc tctgggtaaa tga                                  1413


<210>  12
<211>  470
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized mutagenized mAB 107 IgG4kappa heavy chain V5

<400>  12

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Asp Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val 
            20                  25                  30          


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


Asn Ile Lys Asp Ile Tyr Met Gln Trp Val Arg Gln Ala Pro Gly Gln 
    50                  55                  60                  


Arg Leu Glu Trp Ile Gly Arg Ile Asp Pro Ala Asp Asp Lys Thr Lys 
65                  70                  75                  80  


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


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


Ala Val Tyr Tyr Cys Ala Ser Glu Gly His Tyr Gly Tyr Asp Gly Tyr 
        115                 120                 125             


Ala Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala 
    130                 135                 140                 


Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser 
145                 150                 155                 160 


Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
                165                 170                 175     


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
            180                 185                 190         


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


Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr 
    210                 215                 220                 


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


Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu 
                245                 250                 255     


Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
            260                 265                 270         


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
        275                 280                 285             


Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 
    290                 295                 300                 


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 
305                 310                 315                 320 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
                325                 330                 335     


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 
            340                 345                 350         


Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
        355                 360                 365             


Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn 
    370                 375                 380                 


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
385                 390                 395                 400 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
                405                 410                 415     


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg 
            420                 425                 430         


Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys 
        435                 440                 445             


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
    450                 455                 460                 


Ser Leu Ser Leu Gly Lys 
465                 470 


<210>  13
<211>  21
<212>  PRT
<213>  Artificial

<220>
<223>  Leader sequence

<400>  13

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Asp 
            20      


<210>  14
<211>  726
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized mAb107 IgG4 kappa Light Chain

<400>  14
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt       60

gacgatattg tgatgaccca gagcccggat agcctggcgg tgagcctggg cgaacgcgcg      120

accattaact gcaaaagcag ccagaacctg ctgtatagca gcaaccagaa aaactatctg      180

gcgtggtatc agcagaaacc gggccagccg ccgaaactgc tgatttattg ggcgagcacc      240

cgcgaaagcg gcgtgccgga tcgctttagc ggcagcggca gcggcaccga ttttaccctg      300

accattagca gcctgcaggc ggaagatgtg gcggtgtatt attgccagca gtattatagc      360

tatccgctga cctttggcca gggcaccaaa ctggaaatta aacgtacggt ggctgcacca      420

tctgtcttca tcttcccgcc atctgatgag cagttgaaat ctggaactgc ctctgttgtg      480

tgcctgctga ataacttcta tcccagagag gccaaagtac agtggaaggt ggataacgcc      540

ctccaatcgg gtaactccca ggagagtgtc acagagcagg acagcaagga cagcacctac      600

agcctcagca gcaccctgac gctgagcaaa gcagactacg agaaacacaa agtctacgcc      660

tgcgaagtca cccatcaggg cctgagctca cccgtcacaa agagcttcaa caggggagag      720

tgttag                                                                 726


<210>  15
<211>  260
<212>  PRT
<213>  Artificial

<220>
<223>  scFv of humanized mutated mAb107

<400>  15

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


Gly Ala Ser Val Lys Val Ser Cys Lys Pro Ser Gly Phe Asn Ile Lys 
            20                  25                  30          


Asp Ile Tyr Met Gln Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu 
        35                  40                  45              


Trp Ile Gly Arg Ile Asp Pro Ala Asp Asp Lys Thr Lys Tyr Asp Pro 
    50                  55                  60                  


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


Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Ser Glu Gly His Tyr Gly Tyr Asp Gly Tyr Ala Met Asp 
            100                 105                 110         


Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr 
    130                 135                 140                 


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


Asn Cys Lys Ser Ser Gln Asn Leu Leu Tyr Ser Ser Asn Gln Lys Asn 
                165                 170                 175     


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu 
            180                 185                 190         


Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser 
        195                 200                 205             


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
    210                 215                 220                 


Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr Pro 
225                 230                 235                 240 


Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Glu Asn Leu Tyr 
                245                 250                 255     


Phe Gln Gly Ser 
            260 


<210>  16
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  GS Linker

<400>  16

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  17
<211>  225
<212>  PRT
<213>  Artificial

<220>
<223>  mAb107 IgG1

<400>  17

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


Ser Val Lys Val Ser Cys Lys Pro Ser Gly Phe Asn Ile Lys Asp Ile 
            20                  25                  30          


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


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


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


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


Ala Ser Glu Gly His Tyr Gly Tyr Asp Gly Tyr Ala Met Asp Tyr Trp 
            100                 105                 110         


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


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


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


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


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


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


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


Cys 
225 


<210>  18
<211>  241
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized Light Chain mAb107 IgG4kappa with leader sequence

<400>  18

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln 
        35                  40                  45              


Asn Leu Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln 
    50                  55                  60                  


Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr 
65                  70                  75                  80  


Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 
                85                  90                  95      


Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val 
            100                 105                 110         


Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr Pro Leu Thr Phe Gly Gln Gly 
        115                 120                 125             


Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile 
    130                 135                 140                 


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


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


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


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


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


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


Cys 
    


