                         SEQUENCE LISTING

<110>  BIOMARIN PHARMACEUTICAL INC.
 
<120>  TARGETED THERAPEUTIC LYSOSOMAL ENZYME FUSION PROTEINS, ASSOCIATED
        FORMULATIONS AND USES THEREOF

<130>  30610/50493 PC

<150>  US 62/299,188
<151>  2016-02-24

<150>  US 62/428,221
<151>  2016-11-30

<160>  5     

<170>  PatentIn version 3.5

<210>  1
<211>  720
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  Naglu protein

<400>  1

Asp Glu Ala Arg Glu Ala Ala Ala Val Arg Ala Leu Val Ala Arg Leu 
1               5                   10                  15      


Leu Gly Pro Gly Pro Ala Ala Asp Phe Ser Val Ser Val Glu Arg Ala 
            20                  25                  30          


Leu Ala Ala Lys Pro Gly Leu Asp Thr Tyr Ser Leu Gly Gly Gly Gly 
        35                  40                  45              


Ala Ala Arg Val Arg Val Arg Gly Ser Thr Gly Val Ala Ala Ala Ala 
    50                  55                  60                  


Gly Leu His Arg Tyr Leu Arg Asp Phe Cys Gly Cys His Val Ala Trp 
65                  70                  75                  80  


Ser Gly Ser Gln Leu Arg Leu Pro Arg Pro Leu Pro Ala Val Pro Gly 
                85                  90                  95      


Glu Leu Thr Glu Ala Thr Pro Asn Arg Tyr Arg Tyr Tyr Gln Asn Val 
            100                 105                 110         


Cys Thr Gln Ser Tyr Ser Phe Val Trp Trp Asp Trp Ala Arg Trp Glu 
        115                 120                 125             


Arg Glu Ile Asp Trp Met Ala Leu Asn Gly Ile Asn Leu Ala Leu Ala 
    130                 135                 140                 


Trp Ser Gly Gln Glu Ala Ile Trp Gln Arg Val Tyr Leu Ala Leu Gly 
145                 150                 155                 160 


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


Ala Trp Gly Arg Met Gly Asn Leu His Thr Trp Asp Gly Pro Leu Pro 
            180                 185                 190         


Pro Ser Trp His Ile Lys Gln Leu Tyr Leu Gln His Arg Val Leu Asp 
        195                 200                 205             


Gln Met Arg Ser Phe Gly Met Thr Pro Val Leu Pro Ala Phe Ala Gly 
    210                 215                 220                 


His Val Pro Glu Ala Val Thr Arg Val Phe Pro Gln Val Asn Val Thr 
225                 230                 235                 240 


Lys Met Gly Ser Trp Gly His Phe Asn Cys Ser Tyr Ser Cys Ser Phe 
                245                 250                 255     


Leu Leu Ala Pro Glu Asp Pro Ile Phe Pro Ile Ile Gly Ser Leu Phe 
            260                 265                 270         


Leu Arg Glu Leu Ile Lys Glu Phe Gly Thr Asp His Ile Tyr Gly Ala 
        275                 280                 285             


Asp Thr Phe Asn Glu Met Gln Pro Pro Ser Ser Glu Pro Ser Tyr Leu 
    290                 295                 300                 


Ala Ala Ala Thr Thr Ala Val Tyr Glu Ala Met Thr Ala Val Asp Thr 
305                 310                 315                 320 


Glu Ala Val Trp Leu Leu Gln Gly Trp Leu Phe Gln His Gln Pro Gln 
                325                 330                 335     


Phe Trp Gly Pro Ala Gln Ile Arg Ala Val Leu Gly Ala Val Pro Arg 
            340                 345                 350         


Gly Arg Leu Leu Val Leu Asp Leu Phe Ala Glu Ser Gln Pro Val Tyr 
        355                 360                 365             


Thr Arg Thr Ala Ser Phe Gln Gly Gln Pro Phe Ile Trp Cys Met Leu 
    370                 375                 380                 


His Asn Phe Gly Gly Asn His Gly Leu Phe Gly Ala Leu Glu Ala Val 
385                 390                 395                 400 


Asn Gly Gly Pro Glu Ala Ala Arg Leu Phe Pro Asn Ser Thr Met Val 
                405                 410                 415     


Gly Thr Gly Met Ala Pro Glu Gly Ile Ser Gln Asn Glu Val Val Tyr 
            420                 425                 430         


Ser Leu Met Ala Glu Leu Gly Trp Arg Lys Asp Pro Val Pro Asp Leu 
        435                 440                 445             


Ala Ala Trp Val Thr Ser Phe Ala Ala Arg Arg Tyr Gly Val Ser His 
    450                 455                 460                 


Pro Asp Ala Gly Ala Ala Trp Arg Leu Leu Leu Arg Ser Val Tyr Asn 
465                 470                 475                 480 


Cys Ser Gly Glu Ala Cys Arg Gly His Asn Arg Ser Pro Leu Val Arg 
                485                 490                 495     


Arg Pro Ser Leu Gln Met Asn Thr Ser Ile Trp Tyr Asn Arg Ser Asp 
            500                 505                 510         


Val Phe Glu Ala Trp Arg Leu Leu Leu Thr Ser Ala Pro Ser Leu Ala 
        515                 520                 525             


Thr Ser Pro Ala Phe Arg Tyr Asp Leu Leu Asp Leu Thr Arg Gln Ala 
    530                 535                 540                 


Val Gln Glu Leu Val Ser Leu Tyr Tyr Glu Glu Ala Arg Ser Ala Tyr 
545                 550                 555                 560 


Leu Ser Lys Glu Leu Ala Ser Leu Leu Arg Ala Gly Gly Val Leu Ala 
                565                 570                 575     


Tyr Glu Leu Leu Pro Ala Leu Asp Glu Val Leu Ala Ser Asp Ser Arg 
            580                 585                 590         


Phe Leu Leu Gly Ser Trp Leu Glu Gln Ala Arg Ala Ala Ala Val Ser 
        595                 600                 605             


Glu Ala Glu Ala Asp Phe Tyr Glu Gln Asn Ser Arg Tyr Gln Leu Thr 
    610                 615                 620                 


Leu Trp Gly Pro Glu Gly Asn Ile Leu Asp Tyr Ala Asn Lys Gln Leu 
625                 630                 635                 640 


Ala Gly Leu Val Ala Asn Tyr Tyr Thr Pro Arg Trp Arg Leu Phe Leu 
                645                 650                 655     


Glu Ala Leu Val Asp Ser Val Ala Gln Gly Ile Pro Phe Gln Gln His 
            660                 665                 670         


Gln Phe Asp Lys Asn Val Phe Gln Leu Glu Gln Ala Phe Val Leu Ser 
        675                 680                 685             


Lys Gln Arg Tyr Pro Ser Gln Pro Arg Gly Asp Thr Val Asp Leu Ala 
    690                 695                 700                 


Lys Lys Ile Phe Leu Lys Tyr Tyr Pro Arg Trp Val Ala Gly Ser Trp 
705                 710                 715                 720 


<210>  2
<211>  60
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  AA 8-67 of IGF-II

<400>  2

Leu Cys Gly Gly Glu Leu Val Asp Thr Leu Gln Phe Val Cys Gly Asp 
1               5                   10                  15      


Arg Gly Phe Tyr Phe Ser Arg Pro Ala Ser Arg Val Ser Arg Arg Ser 
            20                  25                  30          


Arg Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala Leu 
        35                  40                  45              


Leu Glu Thr Tyr Cys Ala Thr Pro Ala Lys Ser Glu 
    50                  55                  60  


<210>  3
<211>  60
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide Tag

<400>  3

Leu Cys Gly Gly Glu Leu Val Asp Thr Leu Gln Phe Val Cys Gly Asp 
1               5                   10                  15      


Arg Gly Phe Tyr Phe Ser Arg Pro Ala Ser Arg Val Ser Ala Arg Ser 
            20                  25                  30          


Arg Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala Leu 
        35                  40                  45              


Leu Glu Thr Tyr Cys Ala Thr Pro Ala Lys Ser Glu 
    50                  55                  60  


<210>  4
<211>  31
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Peptide Linker

<400>  4

Gly Ala Pro Gly Gly Gly Ser Pro Ala Pro Ala Pro Thr Pro Ala Pro 
1               5                   10                  15      


Ala Pro Thr Pro Ala Pro Ala Gly Gly Gly Pro Ser Gly Ala Pro 
            20                  25                  30      


<210>  5
<211>  811
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide


<220>
<221>  MISC_FEATURE
<223>  BMN001 therapeutic fusion protein

<400>  5

Asp Glu Ala Arg Glu Ala Ala Ala Val Arg Ala Leu Val Ala Arg Leu 
1               5                   10                  15      


Leu Gly Pro Gly Pro Ala Ala Asp Phe Ser Val Ser Val Glu Arg Ala 
            20                  25                  30          


Leu Ala Ala Lys Pro Gly Leu Asp Thr Tyr Ser Leu Gly Gly Gly Gly 
        35                  40                  45              


Ala Ala Arg Val Arg Val Arg Gly Ser Thr Gly Val Ala Ala Ala Ala 
    50                  55                  60                  


Gly Leu His Arg Tyr Leu Arg Asp Phe Cys Gly Cys His Val Ala Trp 
65                  70                  75                  80  


Ser Gly Ser Gln Leu Arg Leu Pro Arg Pro Leu Pro Ala Val Pro Gly 
                85                  90                  95      


Glu Leu Thr Glu Ala Thr Pro Asn Arg Tyr Arg Tyr Tyr Gln Asn Val 
            100                 105                 110         


Cys Thr Gln Ser Tyr Ser Phe Val Trp Trp Asp Trp Ala Arg Trp Glu 
        115                 120                 125             


Arg Glu Ile Asp Trp Met Ala Leu Asn Gly Ile Asn Leu Ala Leu Ala 
    130                 135                 140                 


Trp Ser Gly Gln Glu Ala Ile Trp Gln Arg Val Tyr Leu Ala Leu Gly 
145                 150                 155                 160 


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


Ala Trp Gly Arg Met Gly Asn Leu His Thr Trp Asp Gly Pro Leu Pro 
            180                 185                 190         


Pro Ser Trp His Ile Lys Gln Leu Tyr Leu Gln His Arg Val Leu Asp 
        195                 200                 205             


Gln Met Arg Ser Phe Gly Met Thr Pro Val Leu Pro Ala Phe Ala Gly 
    210                 215                 220                 


His Val Pro Glu Ala Val Thr Arg Val Phe Pro Gln Val Asn Val Thr 
225                 230                 235                 240 


Lys Met Gly Ser Trp Gly His Phe Asn Cys Ser Tyr Ser Cys Ser Phe 
                245                 250                 255     


Leu Leu Ala Pro Glu Asp Pro Ile Phe Pro Ile Ile Gly Ser Leu Phe 
            260                 265                 270         


Leu Arg Glu Leu Ile Lys Glu Phe Gly Thr Asp His Ile Tyr Gly Ala 
        275                 280                 285             


Asp Thr Phe Asn Glu Met Gln Pro Pro Ser Ser Glu Pro Ser Tyr Leu 
    290                 295                 300                 


Ala Ala Ala Thr Thr Ala Val Tyr Glu Ala Met Thr Ala Val Asp Thr 
305                 310                 315                 320 


Glu Ala Val Trp Leu Leu Gln Gly Trp Leu Phe Gln His Gln Pro Gln 
                325                 330                 335     


Phe Trp Gly Pro Ala Gln Ile Arg Ala Val Leu Gly Ala Val Pro Arg 
            340                 345                 350         


Gly Arg Leu Leu Val Leu Asp Leu Phe Ala Glu Ser Gln Pro Val Tyr 
        355                 360                 365             


Thr Arg Thr Ala Ser Phe Gln Gly Gln Pro Phe Ile Trp Cys Met Leu 
    370                 375                 380                 


His Asn Phe Gly Gly Asn His Gly Leu Phe Gly Ala Leu Glu Ala Val 
385                 390                 395                 400 


Asn Gly Gly Pro Glu Ala Ala Arg Leu Phe Pro Asn Ser Thr Met Val 
                405                 410                 415     


Gly Thr Gly Met Ala Pro Glu Gly Ile Ser Gln Asn Glu Val Val Tyr 
            420                 425                 430         


Ser Leu Met Ala Glu Leu Gly Trp Arg Lys Asp Pro Val Pro Asp Leu 
        435                 440                 445             


Ala Ala Trp Val Thr Ser Phe Ala Ala Arg Arg Tyr Gly Val Ser His 
    450                 455                 460                 


Pro Asp Ala Gly Ala Ala Trp Arg Leu Leu Leu Arg Ser Val Tyr Asn 
465                 470                 475                 480 


Cys Ser Gly Glu Ala Cys Arg Gly His Asn Arg Ser Pro Leu Val Arg 
                485                 490                 495     


Arg Pro Ser Leu Gln Met Asn Thr Ser Ile Trp Tyr Asn Arg Ser Asp 
            500                 505                 510         


Val Phe Glu Ala Trp Arg Leu Leu Leu Thr Ser Ala Pro Ser Leu Ala 
        515                 520                 525             


Thr Ser Pro Ala Phe Arg Tyr Asp Leu Leu Asp Leu Thr Arg Gln Ala 
    530                 535                 540                 


Val Gln Glu Leu Val Ser Leu Tyr Tyr Glu Glu Ala Arg Ser Ala Tyr 
545                 550                 555                 560 


Leu Ser Lys Glu Leu Ala Ser Leu Leu Arg Ala Gly Gly Val Leu Ala 
                565                 570                 575     


Tyr Glu Leu Leu Pro Ala Leu Asp Glu Val Leu Ala Ser Asp Ser Arg 
            580                 585                 590         


Phe Leu Leu Gly Ser Trp Leu Glu Gln Ala Arg Ala Ala Ala Val Ser 
        595                 600                 605             


Glu Ala Glu Ala Asp Phe Tyr Glu Gln Asn Ser Arg Tyr Gln Leu Thr 
    610                 615                 620                 


Leu Trp Gly Pro Glu Gly Asn Ile Leu Asp Tyr Ala Asn Lys Gln Leu 
625                 630                 635                 640 


Ala Gly Leu Val Ala Asn Tyr Tyr Thr Pro Arg Trp Arg Leu Phe Leu 
                645                 650                 655     


Glu Ala Leu Val Asp Ser Val Ala Gln Gly Ile Pro Phe Gln Gln His 
            660                 665                 670         


Gln Phe Asp Lys Asn Val Phe Gln Leu Glu Gln Ala Phe Val Leu Ser 
        675                 680                 685             


Lys Gln Arg Tyr Pro Ser Gln Pro Arg Gly Asp Thr Val Asp Leu Ala 
    690                 695                 700                 


Lys Lys Ile Phe Leu Lys Tyr Tyr Pro Arg Trp Val Ala Gly Ser Trp 
705                 710                 715                 720 


Gly Ala Pro Gly Gly Gly Ser Pro Ala Pro Ala Pro Thr Pro Ala Pro 
                725                 730                 735     


Ala Pro Thr Pro Ala Pro Ala Gly Gly Gly Pro Ser Gly Ala Pro Leu 
            740                 745                 750         


Cys Gly Gly Glu Leu Val Asp Thr Leu Gln Phe Val Cys Gly Asp Arg 
        755                 760                 765             


Gly Phe Tyr Phe Ser Arg Pro Ala Ser Arg Val Ser Ala Arg Ser Arg 
    770                 775                 780                 


Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala Leu Leu 
785                 790                 795                 800 


Glu Thr Tyr Cys Ala Thr Pro Ala Lys Ser Glu 
                805                 810     


