                         SEQUENCE LISTING

<110>  Yeda Research and Development Co. Ltd.
       Ramot at Tel-Aviv University Ltd.
       ARNON, Ruth
       MARON, Ruth
       ARMONY, Gad
       TSOORY, Michael Menachem
       WILCHEK, Meir
       FRENKEL, Dan
 
<120>  METHOD OF TREATING ALZHEIMERS DISEASE

<130>  84728

<150>  IL 270800
<151>  2019-11-20

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  23
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  1

His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His Arg Glu Arg 
1               5                   10                  15      


Met Ser Gln Val Met Arg Glu 
            20              


<210>  2
<211>  18
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  2

Ala Thr Val Ile Val Ile Thr Leu Val Met Leu Lys Lys Lys Gln Tyr 
1               5                   10                  15      


Thr Ser 
        


<210>  3
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  3

Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln Asp 
1               5                   10                  15      


<210>  4
<211>  17
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  4

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


Lys 
    


<210>  5
<211>  54
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  5

His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His Arg Glu Arg 
1               5                   10                  15      


Met Ser Gln Val Met Arg Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Ser Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly 
        35                  40                  45              


Tyr Thr Met His Gln Asp 
    50                  


<210>  6
<211>  54
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic peptides

<400>  6

His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His Arg Glu Arg 
1               5                   10                  15      


Met Ser Gln Val Met Arg Glu Glu Ala Ala Ala Lys Glu Ala Ala Ala 
            20                  25                  30          


Lys Glu Ala Ala Ala Lys Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly 
        35                  40                  45              


Tyr Thr Met His Gln Asp 
    50                  


<210>  7
<211>  770
<212>  PRT
<213>  Homo sapiens

<400>  7

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


Ala Leu Glu Val Pro Thr Asp Gly Asn Ala Gly Leu Leu Ala Glu Pro 
            20                  25                  30          


Gln Ile Ala Met Phe Cys Gly Arg Leu Asn Met His Met Asn Val Gln 
        35                  40                  45              


Asn Gly Lys Trp Asp Ser Asp Pro Ser Gly Thr Lys Thr Cys Ile Asp 
    50                  55                  60                  


Thr Lys Glu Gly Ile Leu Gln Tyr Cys Gln Glu Val Tyr Pro Glu Leu 
65                  70                  75                  80  


Gln Ile Thr Asn Val Val Glu Ala Asn Gln Pro Val Thr Ile Gln Asn 
                85                  90                  95      


Trp Cys Lys Arg Gly Arg Lys Gln Cys Lys Thr His Pro His Phe Val 
            100                 105                 110         


Ile Pro Tyr Arg Cys Leu Val Gly Glu Phe Val Ser Asp Ala Leu Leu 
        115                 120                 125             


Val Pro Asp Lys Cys Lys Phe Leu His Gln Glu Arg Met Asp Val Cys 
    130                 135                 140                 


Glu Thr His Leu His Trp His Thr Val Ala Lys Glu Thr Cys Ser Glu 
145                 150                 155                 160 


Lys Ser Thr Asn Leu His Asp Tyr Gly Met Leu Leu Pro Cys Gly Ile 
                165                 170                 175     


Asp Lys Phe Arg Gly Val Glu Phe Val Cys Cys Pro Leu Ala Glu Glu 
            180                 185                 190         


Ser Asp Asn Val Asp Ser Ala Asp Ala Glu Glu Asp Asp Ser Asp Val 
        195                 200                 205             


Trp Trp Gly Gly Ala Asp Thr Asp Tyr Ala Asp Gly Ser Glu Asp Lys 
    210                 215                 220                 


Val Val Glu Val Ala Glu Glu Glu Glu Val Ala Glu Val Glu Glu Glu 
225                 230                 235                 240 


Glu Ala Asp Asp Asp Glu Asp Asp Glu Asp Gly Asp Glu Val Glu Glu 
                245                 250                 255     


Glu Ala Glu Glu Pro Tyr Glu Glu Ala Thr Glu Arg Thr Thr Ser Ile 
            260                 265                 270         


Ala Thr Thr Thr Thr Thr Thr Thr Glu Ser Val Glu Glu Val Val Arg 
        275                 280                 285             


Glu Val Cys Ser Glu Gln Ala Glu Thr Gly Pro Cys Arg Ala Met Ile 
    290                 295                 300                 


Ser Arg Trp Tyr Phe Asp Val Thr Glu Gly Lys Cys Ala Pro Phe Phe 
305                 310                 315                 320 


Tyr Gly Gly Cys Gly Gly Asn Arg Asn Asn Phe Asp Thr Glu Glu Tyr 
                325                 330                 335     


Cys Met Ala Val Cys Gly Ser Ala Met Ser Gln Ser Leu Leu Lys Thr 
            340                 345                 350         


Thr Gln Glu Pro Leu Ala Arg Asp Pro Val Lys Leu Pro Thr Thr Ala 
        355                 360                 365             


Ala Ser Thr Pro Asp Ala Val Asp Lys Tyr Leu Glu Thr Pro Gly Asp 
    370                 375                 380                 


Glu Asn Glu His Ala His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala 
385                 390                 395                 400 


Lys His Arg Glu Arg Met Ser Gln Val Met Arg Glu Trp Glu Glu Ala 
                405                 410                 415     


Glu Arg Gln Ala Lys Asn Leu Pro Lys Ala Asp Lys Lys Ala Val Ile 
            420                 425                 430         


Gln His Phe Gln Glu Lys Val Glu Ser Leu Glu Gln Glu Ala Ala Asn 
        435                 440                 445             


Glu Arg Gln Gln Leu Val Glu Thr His Met Ala Arg Val Glu Ala Met 
    450                 455                 460                 


Leu Asn Asp Arg Arg Arg Leu Ala Leu Glu Asn Tyr Ile Thr Ala Leu 
465                 470                 475                 480 


Gln Ala Val Pro Pro Arg Pro Arg His Val Phe Asn Met Leu Lys Lys 
                485                 490                 495     


Tyr Val Arg Ala Glu Gln Lys Asp Arg Gln His Thr Leu Lys His Phe 
            500                 505                 510         


Glu His Val Arg Met Val Asp Pro Lys Lys Ala Ala Gln Ile Arg Ser 
        515                 520                 525             


Gln Val Met Thr His Leu Arg Val Ile Tyr Glu Arg Met Asn Gln Ser 
    530                 535                 540                 


Leu Ser Leu Leu Tyr Asn Val Pro Ala Val Ala Glu Glu Ile Gln Asp 
545                 550                 555                 560 


Glu Val Asp Glu Leu Leu Gln Lys Glu Gln Asn Tyr Ser Asp Asp Val 
                565                 570                 575     


Leu Ala Asn Met Ile Ser Glu Pro Arg Ile Ser Tyr Gly Asn Asp Ala 
            580                 585                 590         


Leu Met Pro Ser Leu Thr Glu Thr Lys Thr Thr Val Glu Leu Leu Pro 
        595                 600                 605             


Val Asn Gly Glu Phe Ser Leu Asp Asp Leu Gln Pro Trp His Ser Phe 
    610                 615                 620                 


Gly Ala Asp Ser Val Pro Ala Asn Thr Glu Asn Glu Val Glu Pro Val 
625                 630                 635                 640 


Asp Ala Arg Pro Ala Ala Asp Arg Gly Leu Thr Thr Arg Pro Gly Ser 
                645                 650                 655     


Gly Leu Thr Asn Ile Lys Thr Glu Glu Ile Ser Glu Val Lys Met Asp 
            660                 665                 670         


Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu 
        675                 680                 685             


Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly 
    690                 695                 700                 


Leu Met Val Gly Gly Val Val Ile Ala Thr Val Ile Val Ile Thr Leu 
705                 710                 715                 720 


Val Met Leu Lys Lys Lys Gln Tyr Thr Ser Ile His His Gly Val Val 
                725                 730                 735     


Glu Val Asp Ala Ala Val Thr Pro Glu Glu Arg His Leu Ser Lys Met 
            740                 745                 750         


Gln Gln Asn Gly Tyr Glu Asn Pro Thr Tyr Lys Phe Phe Glu Gln Met 
        755                 760                 765             


Gln Asn 
    770 


<210>  8
<211>  441
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly 
1               5                   10                  15      


Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His 
            20                  25                  30          


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


Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser 
    50                  55                  60                  


Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val 
65                  70                  75                  80  


Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu 
                85                  90                  95      


Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro 
            100                 105                 110         


Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val 
        115                 120                 125             


Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly 
    130                 135                 140                 


Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro 
145                 150                 155                 160 


Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro 
                165                 170                 175     


Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly 
            180                 185                 190         


Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser 
        195                 200                 205             


Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys 
    210                 215                 220                 


Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys 
225                 230                 235                 240 


Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val 
                245                 250                 255     


Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly 
            260                 265                 270         


Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln 
        275                 280                 285             


Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly 
    290                 295                 300                 


Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser 
305                 310                 315                 320 


Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln 
                325                 330                 335     


Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser 
            340                 345                 350         


Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn 
        355                 360                 365             


Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala 
    370                 375                 380                 


Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser 
385                 390                 395                 400 


Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser 
                405                 410                 415     


Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val 
            420                 425                 430         


Ser Ala Ser Leu Ala Lys Gln Gly Leu 
        435                 440     


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

<220>
<223>  cell penetrating peptide (CPP) amino acid sequence

<400>  9

Tyr Gly Arg Lys Lys Arg Arg 
1               5           


<210>  10
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  cell penetrating peptide (CPP) amino acid sequence

<400>  10

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


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

<220>
<223>  cell penetrating peptide (CPP) amino acid sequence

<400>  11

Arg Arg Gln Arg Arg 
1               5   


<210>  12
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  flexible peptide linker

<400>  12

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


<210>  13
<211>  54
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  example of a peptide which comprises an APP derived peptide 
       linked by a flexible peptide linker to a TAU derived peptide

<400>  13

His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His Arg Glu Arg 
1               5                   10                  15      


Met Ser Gln Val Met Arg Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            20                  25                  30          


Ser Gly Gly Gly Gly Ser Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly 
        35                  40                  45              


Tyr Thr Met His Gln Asp 
    50                  


<210>  14
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  example of a rigid peptide linker

<400>  14

Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys 
1               5                   10                  15  


<210>  15
<211>  54
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  example of a peptide which comprises an APP derived peptide 
       linked by a rigid peptide linker to a TAU derived peptide

<400>  15

His Phe Gln Lys Ala Lys Glu Arg Leu Glu Ala Lys His Arg Glu Arg 
1               5                   10                  15      


Met Ser Gln Val Met Arg Glu Glu Ala Ala Ala Lys Glu Ala Ala Ala 
            20                  25                  30          


Lys Glu Ala Ala Ala Lys Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly 
        35                  40                  45              


Tyr Thr Met His Gln Asp 
    50                  


