                         SEQUENCE LISTING

<110>  SPARK THERAPEUTICS, INC.
       ANDERSON, David  W.
       TOTO, Maryann
       DASEN, Sue   E.I.
 
<120>  AAV VECTOR TREATMENT METHODS FOR LATE INFANTILE NEURONAL CEROID 
       LIPOFUSCINOSIS TYPE 2

<130>  023637-0509252

<140>  PCT/US2020/016235
<141>  2020-01-31

<150>  62/800,131
<151>  2019-02-01

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  738
<212>  PRT
<213>  Adeno Associated Virus

<400>  1

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln Lys Gln Asp Asn Gly Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Gln Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 
        115                 120                 125             


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


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


Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 
                165                 170                 175     


Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro 
            180                 185                 190         


Pro Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly 
        195                 200                 205             


Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 
    210                 215                 220                 


Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 
225                 230                 235                 240 


Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 
                245                 250                 255     


Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 
            260                 265                 270         


Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 
        275                 280                 285             


Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 
    290                 295                 300                 


Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 
305                 310                 315                 320 


Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 
                325                 330                 335     


Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 
            340                 345                 350         


Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 
        355                 360                 365             


Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 
    370                 375                 380                 


Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 
385                 390                 395                 400 


Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 
                405                 410                 415     


Asn Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 
            420                 425                 430         


Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 
        435                 440                 445             


Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu 
    450                 455                 460                 


Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp 
465                 470                 475                 480 


Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser 
                485                 490                 495     


Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 
            500                 505                 510         


Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 
        515                 520                 525             


His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 
    530                 535                 540                 


Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 
545                 550                 555                 560 


Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 
                565                 570                 575     


Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala 
            580                 585                 590         


Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val 
        595                 600                 605             


Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 
    610                 615                 620                 


Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 
625                 630                 635                 640 


Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val 
                645                 650                 655     


Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ala Lys Leu Ala Ser Phe 
            660                 665                 670         


Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu 
        675                 680                 685             


Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr 
    690                 695                 700                 


Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu 
705                 710                 715                 720 


Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 
                725                 730                 735     


Asn Leu 
        


<210>  2
<211>  736
<212>  PRT
<213>  Adeno Associated Virus

<400>  2

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Ala Leu Gln Pro Gly Ala Pro Lys Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Asp Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Val Gly 
145                 150                 155                 160 


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


Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Thr Ser Leu Gly Ser Asn Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr 
            260                 265                 270         


Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 
        275                 280                 285             


Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp 
    290                 295                 300                 


Gly Phe Arg Pro Lys Lys Leu Ser Phe Lys Leu Phe Asn Ile Gln Val 
305                 310                 315                 320 


Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 
                325                 330                 335     


Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr 
            340                 345                 350         


Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp 
        355                 360                 365             


Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 
    370                 375                 380                 


Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 
385                 390                 395                 400 


Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe Glu 
                405                 410                 415     


Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg 
            420                 425                 430         


Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg Thr 
        435                 440                 445             


Gln Gly Thr Thr Ser Gly Thr Thr Asn Gln Ser Arg Leu Leu Phe Ser 
    450                 455                 460                 


Gln Ala Gly Pro Gln Ser Met Ser Leu Gln Ala Arg Asn Trp Leu Pro 
465                 470                 475                 480 


Gly Pro Cys Tyr Arg Gln Gln Arg Leu Ser Lys Thr Ala Asn Asp Asn 
                485                 490                 495     


Asn Asn Ser Asn Phe Pro Trp Thr Ala Ala Ser Lys Tyr His Leu Asn 
            500                 505                 510         


Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys 
        515                 520                 525             


Asp Asp Glu Glu Lys Phe Phe Pro Met His Gly Asn Leu Ile Phe Gly 
    530                 535                 540                 


Lys Glu Gly Thr Thr Ala Ser Asn Ala Glu Leu Asp Asn Val Met Ile 
545                 550                 555                 560 


Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln 
                565                 570                 575     


Tyr Gly Thr Val Ala Asn Asn Leu Gln Ser Ser Asn Thr Ala Pro Thr 
            580                 585                 590         


Thr Arg Thr Val Asn Asp Gln Gly Ala Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 
625                 630                 635                 640 


Lys His Pro Pro Pro Gln Ile Met Ile Lys Asn Thr Pro Val Pro Ala 
                645                 650                 655     


Asn Pro Pro Thr Thr Phe Ser Pro Ala Lys Phe Ala Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val 
705                 710                 715                 720 


Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 
                725                 730                 735     


<210>  3
<211>  1672
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CAG Promoter Sequence

<400>  3
atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg cctggctgac       60

cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata gtaacgccaa      120

tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc cacttggcag      180

tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac ggtaaatggc      240

ccgcctggca ttatgcccag tacatgacct tatgggactt tcctacttgg cagtacatct      300

acgtattagt catcgctatt accatggtcg aggtgagccc cacgttctgc ttcactctcc      360

ccatctcccc cccctcccca cccccaattt tgtatttatt tattttttaa ttattttgtg      420

cagcgatggg ggcggggggg gggggggggc gcgcgccagg cggggcgggg cggggcgagg      480

ggcggggcgg ggcgaggcgg agaggtgcgg cggcagccaa tcagagcggc gcgctccgaa      540

agtttccttt tatggcgagg cggcggcggc ggcggcccta taaaaagcga agcgcgcggc      600

gggcggggag tcgctgcgac gctgccttcg ccccgtgccc cgctccgccg ccgcctcgcg      660

ccgcccgccc cggctctgac tgaccgcgtt actcccacag gtgagcgggc gggacggccc      720

ttctcctccg ggctgtaatt agcgcttggt ttaatgacgg cttgtttctt ttctgtggct      780

gcgtgaaagc cttgaggggc tccgggaggg ccctttgtgc ggggggagcg gctcgggggg      840

tgcgtgcgtg tgtgtgtgcg tggggagcgc cgcgtgcggc tccgcgctgc ccggcggctg      900

tgagcgctgc gggcgcggcg cggggctttg tgcgctccgc agtgtgcgcg aggggagcgc      960

ggccgggggc ggtgccccgc ggtgcggggg gggctgcgag gggaacaaag gctgcgtgcg     1020

gggtgtgtgc gtgggggggt gagcaggggg tgtgggcgcg tcggtcgggc tgcaaccccc     1080

cctgcacccc cctccccgag ttgctgagca cggcccggct tcgggtgcgg ggctccgtac     1140

ggggcgtggc gcggggctcg ccgtgccggg cggggggtgg cggcaggtgg gggtgccggg     1200

cggggcgggg ccgcctcggg ccggggaggg ctcgggggag gggcgcggcg gcccccggag     1260

cgccggcggc tgtcgaggcg cggcgagccg cagccattgc cttttatggt aatcgtgcga     1320

gagggcgcag ggacttcctt tgtcccaaat ctgtgcggag ccgaaatctg ggaggcgccg     1380

ccgcaccccc tctagcgggc gcggggcgaa gcggtgcggc gccggcagga aggaaatggg     1440

cggggagggc cttcgtgcgt cgccgcgccg ccgtcccctt ctccctctcc agcctcgggg     1500

ctgtccgcgg ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg     1560

gcgtgtgacc ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct     1620

acagctcctg ggcaacgtgc tggttattgt gctgtctcat cattttggca aa             1672


<210>  4
<211>  563
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Gly Leu Gln Ala Cys Leu Leu Gly Leu Phe Ala Leu Ile Leu Ser 
1               5                   10                  15      


Gly Lys Cys Ser Tyr Ser Pro Glu Pro Asp Gln Arg Arg Thr Leu Pro 
            20                  25                  30          


Pro Gly Trp Val Ser Leu Gly Arg Ala Asp Pro Glu Glu Glu Leu Ser 
        35                  40                  45              


Leu Thr Phe Ala Leu Arg Gln Gln Asn Val Glu Arg Leu Ser Glu Leu 
    50                  55                  60                  


Val Gln Ala Val Ser Asp Pro Ser Ser Pro Gln Tyr Gly Lys Tyr Leu 
65                  70                  75                  80  


Thr Leu Glu Asn Val Ala Asp Leu Val Arg Pro Ser Pro Leu Thr Leu 
                85                  90                  95      


His Thr Val Gln Lys Trp Leu Leu Ala Ala Gly Ala Gln Lys Cys His 
            100                 105                 110         


Ser Val Ile Thr Gln Asp Phe Leu Thr Cys Trp Leu Ser Ile Arg Gln 
        115                 120                 125             


Ala Glu Leu Leu Leu Pro Gly Ala Glu Phe His His Tyr Val Gly Gly 
    130                 135                 140                 


Pro Thr Glu Thr His Val Val Arg Ser Pro His Pro Tyr Gln Leu Pro 
145                 150                 155                 160 


Gln Ala Leu Ala Pro His Val Asp Phe Val Gly Gly Leu His Arg Phe 
                165                 170                 175     


Pro Pro Thr Ser Ser Leu Arg Gln Arg Pro Glu Pro Gln Val Thr Gly 
            180                 185                 190         


Thr Val Gly Leu His Leu Gly Val Thr Pro Ser Val Ile Arg Lys Arg 
        195                 200                 205             


Tyr Asn Leu Thr Ser Gln Asp Val Gly Ser Gly Thr Ser Asn Asn Ser 
    210                 215                 220                 


Gln Ala Cys Ala Gln Phe Leu Glu Gln Tyr Phe His Asp Ser Asp Leu 
225                 230                 235                 240 


Ala Gln Phe Met Arg Leu Phe Gly Gly Asn Phe Ala His Gln Ala Ser 
                245                 250                 255     


Val Ala Arg Val Val Gly Gln Gln Gly Arg Gly Arg Ala Gly Ile Glu 
            260                 265                 270         


Ala Ser Leu Asp Val Gln Tyr Leu Met Ser Ala Gly Ala Asn Ile Ser 
        275                 280                 285             


Thr Trp Val Tyr Ser Ser Pro Gly Arg His Glu Gly Gln Glu Pro Phe 
    290                 295                 300                 


Leu Gln Trp Leu Met Leu Leu Ser Asn Glu Ser Ala Leu Pro His Val 
305                 310                 315                 320 


His Thr Val Ser Tyr Gly Asp Asp Glu Asp Ser Leu Ser Ser Ala Tyr 
                325                 330                 335     


Ile Gln Arg Val Asn Thr Glu Leu Met Lys Ala Ala Ala Arg Gly Leu 
            340                 345                 350         


Thr Leu Leu Phe Ala Ser Gly Asp Ser Gly Ala Gly Cys Trp Ser Val 
        355                 360                 365             


Ser Gly Arg His Gln Phe Arg Pro Thr Phe Pro Ala Ser Ser Pro Tyr 
    370                 375                 380                 


Val Thr Thr Val Gly Gly Thr Ser Phe Gln Glu Pro Phe Leu Ile Thr 
385                 390                 395                 400 


Asn Glu Ile Val Asp Tyr Ile Ser Gly Gly Gly Phe Ser Asn Val Phe 
                405                 410                 415     


Pro Arg Pro Ser Tyr Gln Glu Glu Ala Val Thr Lys Phe Leu Ser Ser 
            420                 425                 430         


Ser Pro His Leu Pro Pro Ser Ser Tyr Phe Asn Ala Ser Gly Arg Ala 
        435                 440                 445             


Tyr Pro Asp Val Ala Ala Leu Ser Asp Gly Tyr Trp Val Val Ser Asn 
    450                 455                 460                 


Arg Val Pro Ile Pro Trp Val Ser Gly Thr Ser Ala Ser Thr Pro Val 
465                 470                 475                 480 


Phe Gly Gly Ile Leu Ser Leu Ile Asn Glu His Arg Ile Leu Ser Gly 
                485                 490                 495     


Arg Pro Pro Leu Gly Phe Leu Asn Pro Arg Leu Tyr Gln Gln His Gly 
            500                 505                 510         


Ala Gly Leu Phe Asp Val Thr Arg Gly Cys His Glu Ser Cys Leu Asp 
        515                 520                 525             


Glu Glu Val Glu Gly Gln Gly Phe Cys Ser Gly Pro Gly Trp Asp Pro 
    530                 535                 540                 


Val Thr Gly Trp Gly Thr Pro Asn Phe Pro Ala Leu Leu Lys Thr Leu 
545                 550                 555                 560 


Leu Asn Pro 
            


