                         SEQUENCE LISTING

<110>  Yeda Research and Development Co. Ltd.
       YARDEN, Yosef
       MANCINI, Maicol
       GABORIT, Nadege
 
<120>  COMPOSITIONS AND METHODS FOR TREATING CANCER RESISTANT TO A 
       TYROSINE KINASE INHIBITOR (TKI)

<130>  63478

<150>  US 62/047,150
<151>  2014-09-08

<160>  32    

<170>  PatentIn version 3.5

<210>  1
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-EGFR 565  VH amino acid sequence

<400>  1

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


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


Trp Ile His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Glu Ile Gly Pro Ile Asn Gly Arg Ser Asn Tyr Ile Glu Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Glu Asp Asp Tyr Asp Gly Lys Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser 
        115                 120 


<210>  2
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  EGFR 565  kappa amino acid sequence


<220>
<221>  misc_feature
<222>  (11)..(11)
<223>  Xaa can be any naturally occurring amino acid

<400>  2

Asp Ile Val Met Thr Gln Ser His Lys Phe Xaa Ser Thr Ser Val Gly 
1               5                   10                  15      


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


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


Tyr Trp Thr Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 
    50                  55                  60                  


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


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


Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg 
            100                 105     


<210>  3
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  of anti-HER2 N12 VH amino acid sequence

<400>  3

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


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


Trp Met Tyr Trp Ile Lys Gln Arg Pro Asp Gln Gly Leu Glu Ser Ile 
        35                  40                  45              


Gly Asn Ile His Pro Asn Asn Gly Gly Thr Asn Tyr Ser Gly Lys Phe 
    50                  55                  60                  


Lys Asn Lys Ala Ser Leu Thr Val Asp Lys Ser Ser Thr 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 Leu Thr Gly Ile Gly Met Asp Tyr Trp Gly Gln Gly Thr Ser 
            100                 105                 110         


Val Ile Val Ser Ser 
        115         


<210>  4
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-HER2 N12 Vkappa amino acid sequence

<400>  4

Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly 
1               5                   10                  15      


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


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


Tyr Trp Thr Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 
    50                  55                  60                  


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


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


Gly Gly Gly Thr Arg Leu Glu Ile Lys Leu 
            100                 105     


<210>  5
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-HER3 33 VH amino acid sequence

<400>  5

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


Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly 
            20                  25                  30          


Phe Tyr Trp Ser Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp 
        35                  40                  45              


Met Gly Tyr Ile Ala Tyr Asp Gly Thr Ser Asn Tyr Asn Pro Ser Leu 
    50                  55                  60                  


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


Leu Lys Leu Lys Ser Val Thr Asn Glu Asp Thr Pro Thr Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Gly Gly Tyr Tyr Gly Gln Leu Leu Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser 
        115                 120 


<210>  6
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-HER3 33 Vkappa amino acid sequence

<400>  6

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


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


Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Val Leu Ile 
        35                  40                  45              


Tyr Asn Thr Ala Lys Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Gly Lys Thr Leu Pro Trp 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys 
            100                 105         


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

<220>
<223>  Single strand DNA oligonucleotide

<400>  7
gaggtggtac ttcaattgcg actca                                             25


<210>  8
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  8
agggaaggcg gacgcctgat                                                   20


<210>  9
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  9
tgcagtggat tcgagaagc                                                    19


<210>  10
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  10
agttcaacat gacgaagatg                                                   20


<210>  11
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  11
acagttgcca tgtagacc                                                     18


<210>  12
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  12
tttttggttg agcacagg                                                     18


<210>  13
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  13
ggcgtcccgg cgctaggaag gcctgcgcag agag                                   34


<210>  14
<211>  36
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Single strand DNA oligonucleotide

<400>  14
ctctcttcgc gcaggccttc ctagcgccgg gacgcc                                 36


<210>  15
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  15

Gly Tyr Thr Phe Thr Asn Tyr Trp 
1               5               


<210>  16
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  16

Ile Gly Pro Ile Asn Gly Arg Ser 
1               5               


<210>  17
<211>  13
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  17

Ala Arg Glu Asp Asp Tyr Asp Gly Lys Ala Met Asp Tyr 
1               5                   10              


<210>  18
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  18

Gln Asn Val Gly Thr Ala 
1               5       


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

<220>
<223>  CDR peptide sequence

<400>  19

Trp Thr Ser 
1           


<210>  20
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  20

Gln Gln Tyr Ser Gly Tyr Ser 
1               5           


<210>  21
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  21

Gly Tyr Thr Phe Thr Ser Tyr Trp 
1               5               


<210>  22
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  22

Ile His Pro Asn Asn Gly Gly Thr 
1               5               


<210>  23
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  23

Ala Arg Leu Thr Gly Ile Gly Met Asp Tyr 
1               5                   10  


<210>  24
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  24

Gln Asn Val Gly Thr Ala 
1               5       


<210>  25
<211>  3
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  25

Trp Thr Ser 
1           


<210>  26
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  26

Gln Gln Tyr Ser Gly Tyr Ser 
1               5           


<210>  27
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  27

Gly Tyr Ser Ile Thr Ser Gly Phe Tyr 
1               5                   


<210>  28
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  28

Ile Ala Tyr Asp Gly Thr Ser 
1               5           


<210>  29
<211>  13
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  29

Ala Arg Gly Gly Gly Tyr Tyr Gly Gln Leu Leu Asp Tyr 
1               5                   10              


<210>  30
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CDR peptide sequence

<400>  30

Gln Asp Ile Ser Asn Tyr 
1               5       


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

<220>
<223>  CDR peptide sequence

<400>  31

Asn Thr Ala 
1           


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

<220>
<223>  CDR peptide sequence

<400>  32

Gln Gln Gly Lys Thr Leu Pro Trp Thr 
1               5                   


