                         SEQUENCE LISTING

<110>  SOERENSEN, Morten Draeby
       HOFF, Kirsten
 
<120>  CHIMERIC ANTI-HUMAN BRAF V600E ANTIBODIES AND METHODS FOR MAKING 
       AND USING THEM

<130>  6363.138510PCT

<140>  to be assigned
<141>  2021-11-15

<150>  US 63/114,123
<151>  2020-11-16

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  456
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Heavy chain with signal peptide

<400>  1

Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly 
1               5                   10                  15      


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


Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 
        35                  40                  45              


Thr Ser Tyr Asn Met His Trp Ile Lys Gln Thr Pro Arg Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn 
65                  70                  75                  80  


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn 
                85                  90                  95      


Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 
            100                 105                 110         


Tyr Phe Cys Ala Arg Asp Gly Ile Ser Pro Trp Gly Gln Gly Thr Leu 
        115                 120                 125             


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


Ala Pro Cys Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys 
145                 150                 155                 160 


Leu Val Lys Gly Tyr Leu Pro Glu Pro Val Thr Val Thr Trp Asn Ser 
                165                 170                 175     


Gly Thr Leu Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser 
            180                 185                 190         


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser 
        195                 200                 205             


Gln Pro Val Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val 
    210                 215                 220                 


Asp Lys Thr Val Ala Pro Ser Thr Cys Ser Lys Pro Thr Cys Pro Pro 
225                 230                 235                 240 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro 
                245                 250                 255     


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            260                 265                 270         


Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile 
        275                 280                 285             


Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln 
    290                 295                 300                 


Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln 
305                 310                 315                 320 


Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala 
                325                 330                 335     


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


Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser 
        355                 360                 365             


Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser 
    370                 375                 380                 


Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr 
385                 390                 395                 400 


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


Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe 
            420                 425                 430         


Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        435                 440                 445             


Ser Ile Ser Arg Ser Pro Gly Lys 
    450                 455     


<210>  2
<211>  437
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Heavy chain without signal peptide

<400>  2

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


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


Asn Met His Trp Ile Lys Gln Thr Pro Arg Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


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


Lys Gly Lys Ala Thr Leu Thr Val Asp Arg Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  


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


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


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


Cys Gly Asp Thr Pro Ser Ser Thr Val Thr Leu Gly Cys Leu Val Lys 
    130                 135                 140                 


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


Thr Asn Gly Val Arg Thr Phe Pro Ser Val Arg Gln Ser Ser Gly Leu 
                165                 170                 175     


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


Thr Cys Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr 
        195                 200                 205             


Val Ala Pro Ser Thr Cys Ser Lys Pro Thr Cys Pro Pro Pro Glu Leu 
    210                 215                 220                 


Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr 
225                 230                 235                 240 


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


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


Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser 
        275                 280                 285             


Thr Ile Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu 
    290                 295                 300                 


Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala 
305                 310                 315                 320 


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


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


Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser 
        355                 360                 365             


Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr 
    370                 375                 380                 


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


Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser 
                405                 410                 415     


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


Arg Ser Pro Gly Lys 
        435         


<210>  3
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: rabbit IgG heavy chain signal peptide

<400>  3

Met Glu Thr Gly Leu Arg Trp Leu Leu Leu Val Ala Val Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys 
            


<210>  4
<211>  323
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: the rabbit IgG heavy chain constant domain

<400>  4

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


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


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


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


Leu Ser Ser Val Val Ser Val Thr Ser Ser Ser Gln Pro Val Thr Cys 
65                  70                  75                  80  


Asn Val Ala His Pro Ala Thr Asn Thr Lys Val Asp Lys Thr Val Ala 
                85                  90                  95      


Pro Ser Thr Cys Ser Lys Pro Thr Cys Pro Pro Pro Glu Leu Leu Gly 
            100                 105                 110         


Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
        115                 120                 125             


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


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


Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn Ser Thr Ile 
                165                 170                 175     


Arg Val Val Ser Thr Leu Pro Ile Ala His Gln Asp Trp Leu Arg Gly 
            180                 185                 190         


Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro Ala Pro Ile 
        195                 200                 205             


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


Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg Ser Val Ser 
225                 230                 235                 240 


Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile Ser Val Glu 
                245                 250                 255     


Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr Thr Pro Ala 
            260                 265                 270         


Val Leu Asp Ser Asp Gly Ser Tyr Phe Leu Tyr Ser Lys Leu Ser Val 
        275                 280                 285             


Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys Ser Val Met 
    290                 295                 300                 


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile Ser Arg Ser 
305                 310                 315                 320 


Pro Gly Lys 
            


<210>  5
<211>  233
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Light chain with signal peptide

<400>  5

Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Pro Gly Ala Thr Phe Asp Ile Lys Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Met Tyr Ala Ser Leu Gly Glu Arg Val Thr Ile Thr Cys Lys Ala Ser 
        35                  40                  45              


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


Ser Pro Lys Thr Leu Ile Tyr Arg Ala Asn Arg Val Leu Asp Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Gln Asp Tyr Ser Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Glu Ser Glu Asp Met Gly Ile Tyr Tyr Cys Leu His 
            100                 105                 110         


Tyr Asp Glu Tyr Pro Tyr Thr Tyr Gly Gly Gly Thr Lys Leu Glu Ile 
        115                 120                 125             


Lys Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro Pro Ala Ala 
    130                 135                 140                 


Asp Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val Ala Asn Lys 
145                 150                 155                 160 


Tyr Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly Thr Thr Gln 
                165                 170                 175     


Thr Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser Ala Asp Cys 
            180                 185                 190         


Thr Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr Gln Tyr Asn 
        195                 200                 205             


Ser His Lys Glu Tyr Thr Cys Lys Val Thr Gln Gly Thr Thr Ser Val 
    210                 215                 220                 


Val Gln Ser Phe Asn Arg Gly Asp Cys 
225                 230             


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

<220>
<223>  Synthetic: Light chain without signal peptide

<400>  6

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


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


Leu Ser Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Thr Leu Ile 
        35                  40                  45              


Tyr Arg Ala Asn Arg Val Leu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Gln Asp Tyr Ser Leu Thr Ile Ser Ser Leu Glu Ser 
65                  70                  75                  80  


Glu Asp Met Gly Ile Tyr Tyr Cys Leu His Tyr Asp Glu Tyr Pro Tyr 
                85                  90                  95      


Thr Tyr Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly Asp Pro Val Ala 
            100                 105                 110         


Pro Thr Val Leu Ile Phe Pro Pro Ala Ala Asp Gln Val Ala Thr Gly 
        115                 120                 125             


Thr Val Thr Ile Val Cys Val Ala Asn Lys Tyr Phe Pro Asp Val Thr 
    130                 135                 140                 


Val Thr Trp Glu Val Asp Gly Thr Thr Gln Thr Thr Gly Ile Glu Asn 
145                 150                 155                 160 


Ser Lys Thr Pro Gln Asn Ser Ala Asp Cys Thr Tyr Asn Leu Ser Ser 
                165                 170                 175     


Thr Leu Thr Leu Thr Ser Thr Gln Tyr Asn Ser His Lys Glu Tyr Thr 
            180                 185                 190         


Cys Lys Val Thr Gln Gly Thr Thr Ser Val Val Gln Ser Phe Asn Arg 
        195                 200                 205             


Gly Asp Cys 
    210     


<210>  7
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: the rabbit IgG heavy chain signal peptide

<400>  7

Met Asp Thr Arg Ala Pro Thr Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Pro Gly Ala Thr Phe 
            20          


<210>  8
<211>  104
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: rabbit kappa1 light chain constant domain

<400>  8

Gly Asp Pro Val Ala Pro Thr Val Leu Ile Phe Pro Pro Ala Ala Asp 
1               5                   10                  15      


Gln Val Ala Thr Gly Thr Val Thr Ile Val Cys Val Ala Asn Lys Tyr 
            20                  25                  30          


Phe Pro Asp Val Thr Val Thr Trp Glu Val Asp Gly Thr Thr Gln Thr 
        35                  40                  45              


Thr Gly Ile Glu Asn Ser Lys Thr Pro Gln Asn Ser Ala Asp Cys Thr 
    50                  55                  60                  


Tyr Asn Leu Ser Ser Thr Leu Thr Leu Thr Ser Thr Gln Tyr Asn Ser 
65                  70                  75                  80  


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


Gln Ser Phe Asn Arg Gly Asp Cys 
            100                 


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

<220>
<223>  Synthetic: CDR1

<400>  9

Gly Tyr Thr Phe Thr Ser Tyr Asn 
1               5               


<210>  10
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: CDR2

<400>  10

Ile Tyr Pro Gly Asn Gly Asp Thr 
1               5               


<210>  11
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: CDR3

<400>  11

Ala Arg Asp Gly Ile Ser Pro 
1               5           


<210>  12
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: CDR1

<400>  12

Gln Asp Ile Asn Arg Tyr 
1               5       


<210>  13
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: CDR2

<400>  13

Arg Ala Asn 
1           


<210>  14
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: CDR3

<400>  14

Leu His Tyr Asp Glu Tyr Pro Tyr Thr 
1               5                   


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

<220>
<223>  Synthetic: polyglycine linker


<220>
<221>  SITE
<222>  (9)..(16)
<223>  "Gly Gly Gly Ser" may or may not be present

<400>  15

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


<210>  16
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: 6xHis tag

<400>  16

His His His His His His 
1               5       


<210>  17
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Recombinant antibody specifically targeting the BRAF 
       V600E mutation

<400>  17

Gly Leu Ala Thr Glu Lys Ser Arg Trp Ser Gly 
1               5                   10      


