                               SEQUENCE LISTING

<110> ALEXION PHARMACEUTICALS, INC.
 
<120> TREATING SEIZURE WITH RECOMBINANT ALKALINE PHOSPHATASE

<130> 0239 PCT

<140>
<141>

<150> 62/259,307
<151> 2015-11-24

<150> 62/088,025
<151> 2014-12-05

<160> 4     

<170> PatentIn version 3.5

<210> 1
<211> 743
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 1
Met Ile Ser Pro Phe Leu Val Leu Ala Ile Gly Thr Cys Leu Thr Asn 
1               5                   10                  15      


Ser Leu Val Pro Glu Lys Glu Lys Asp Pro Lys Tyr Trp Arg Asp Gln 
            20                  25                  30          


Ala Gln Glu Thr Leu Lys Tyr Ala Leu Glu Leu Gln Lys Leu Asn Thr 
        35                  40                  45              


Asn Val Ala Lys Asn Val Ile Met Phe Leu Gly Asp Gly Met Gly Val 
    50                  55                  60                  


Ser Thr Val Thr Ala Ala Arg Ile Leu Lys Gly Gln Leu His His Asn 
65                  70                  75                  80  


Pro Gly Glu Glu Thr Arg Leu Glu Met Asp Lys Phe Pro Phe Val Ala 
                85                  90                  95      


Leu Ser Lys Thr Tyr Asn Thr Asn Ala Gln Val Pro Asp Ser Ala Gly 
            100                 105                 110         


Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Glu Gly Thr Val 
        115                 120                 125             


Gly Val Ser Ala Ala Thr Glu Arg Ser Arg Cys Asn Thr Thr Gln Gly 
    130                 135                 140                 


Asn Glu Val Thr Ser Ile Leu Arg Trp Ala Lys Asp Ala Gly Lys Ser 
145                 150                 155                 160 


Val Gly Ile Val Thr Thr Thr Arg Val Asn His Ala Thr Pro Ser Ala 
                165                 170                 175     


Ala Tyr Ala His Ser Ala Asp Arg Asp Trp Tyr Ser Asp Asn Glu Met 
            180                 185                 190         


Pro Pro Glu Ala Leu Ser Gln Gly Cys Lys Asp Ile Ala Tyr Gln Leu 
        195                 200                 205             


Met His Asn Ile Arg Asp Ile Asp Val Ile Met Gly Gly Gly Arg Lys 
    210                 215                 220                 


Tyr Met Tyr Pro Lys Asn Lys Thr Asp Val Glu Tyr Glu Ser Asp Glu 
225                 230                 235                 240 


Lys Ala Arg Gly Thr Arg Leu Asp Gly Leu Asp Leu Val Asp Thr Trp 
                245                 250                 255     


Lys Ser Phe Lys Pro Arg Tyr Lys His Ser His Phe Ile Trp Asn Arg 
            260                 265                 270         


Thr Glu Leu Leu Thr Leu Asp Pro His Asn Val Asp Tyr Leu Leu Gly 
        275                 280                 285             


Leu Phe Glu Pro Gly Asp Met Gln Tyr Glu Leu Asn Arg Asn Asn Val 
    290                 295                 300                 


Thr Asp Pro Ser Leu Ser Glu Met Val Val Val Ala Ile Gln Ile Leu 
305                 310                 315                 320 


Arg Lys Asn Pro Lys Gly Phe Phe Leu Leu Val Glu Gly Gly Arg Ile 
                325                 330                 335     


Asp His Gly His His Glu Gly Lys Ala Lys Gln Ala Leu His Glu Ala 
            340                 345                 350         


Val Glu Met Asp Arg Ala Ile Gly Gln Ala Gly Ser Leu Thr Ser Ser 
        355                 360                 365             


Glu Asp Thr Leu Thr Val Val Thr Ala Asp His Ser His Val Phe Thr 
    370                 375                 380                 


Phe Gly Gly Tyr Thr Pro Arg Gly Asn Ser Ile Phe Gly Leu Ala Pro 
385                 390                 395                 400 


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


Asn Gly Pro Gly Tyr Lys Val Val Gly Gly Glu Arg Glu Asn Val Ser 
            420                 425                 430         


Met Val Asp Tyr Ala His Asn Asn Tyr Gln Ala Gln Ser Ala Val Pro 
        435                 440                 445             


Leu Arg His Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ser Lys 
    450                 455                 460                 


Gly Pro Met Ala His Leu Leu His Gly Val His Glu Gln Asn Tyr Val 
465                 470                 475                 480 


Pro His Val Met Ala Tyr Ala Ala Cys Ile Gly Ala Asn Leu Gly His 
                485                 490                 495     


Cys Ala Pro Ala Ser Ser Leu Lys Asp Lys Thr His Thr Cys Pro Pro 
            500                 505                 510         


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
        515                 520                 525             


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
    530                 535                 540                 


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
545                 550                 555                 560 


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
                565                 570                 575     


Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
            580                 585                 590         


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
        595                 600                 605             


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
    610                 615                 620                 


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
625                 630                 635                 640 


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                645                 650                 655     


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
            660                 665                 670         


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
        675                 680                 685             


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
    690                 695                 700                 


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
705                 710                 715                 720 


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Asp Ile Asp Asp Asp 
                725                 730                 735     


Asp Asp Asp Asp Asp Asp Asp 
            740             


<210> 2
<211> 485
<212> PRT
<213> Homo sapiens

<400> 2
Leu Val Pro Glu Lys Glu Lys Asp Pro Lys Tyr Trp Arg Asp Gln Ala 
1               5                   10                  15      


Gln Glu Thr Leu Lys Tyr Ala Leu Glu Leu Gln Lys Leu Asn Thr Asn 
            20                  25                  30          


Val Ala Lys Asn Val Ile Met Phe Leu Gly Asp Gly Met Gly Val Ser 
        35                  40                  45              


Thr Val Thr Ala Ala Arg Ile Leu Lys Gly Gln Leu His His Asn Pro 
    50                  55                  60                  


Gly Glu Glu Thr Arg Leu Glu Met Asp Lys Phe Pro Phe Val Ala Leu 
65                  70                  75                  80  


Ser Lys Thr Tyr Asn Thr Asn Ala Gln Val Pro Asp Ser Ala Gly Thr 
                85                  90                  95      


Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Glu Gly Thr Val Gly 
            100                 105                 110         


Val Ser Ala Ala Thr Glu Arg Ser Arg Cys Asn Thr Thr Gln Gly Asn 
        115                 120                 125             


Glu Val Thr Ser Ile Leu Arg Trp Ala Lys Asp Ala Gly Lys Ser Val 
    130                 135                 140                 


Gly Ile Val Thr Thr Thr Arg Val Asn His Ala Thr Pro Ser Ala Ala 
145                 150                 155                 160 


Tyr Ala His Ser Ala Asp Arg Asp Trp Tyr Ser Asp Asn Glu Met Pro 
                165                 170                 175     


Pro Glu Ala Leu Ser Gln Gly Cys Lys Asp Ile Ala Tyr Gln Leu Met 
            180                 185                 190         


His Asn Ile Arg Asp Ile Asp Val Ile Met Gly Gly Gly Arg Lys Tyr 
        195                 200                 205             


Met Tyr Pro Lys Asn Lys Thr Asp Val Glu Tyr Glu Ser Asp Glu Lys 
    210                 215                 220                 


Ala Arg Gly Thr Arg Leu Asp Gly Leu Asp Leu Val Asp Thr Trp Lys 
225                 230                 235                 240 


Ser Phe Lys Pro Arg Tyr Lys His Ser His Phe Ile Trp Asn Arg Thr 
                245                 250                 255     


Glu Leu Leu Thr Leu Asp Pro His Asn Val Asp Tyr Leu Leu Gly Leu 
            260                 265                 270         


Phe Glu Pro Gly Asp Met Gln Tyr Glu Leu Asn Arg Asn Asn Val Thr 
        275                 280                 285             


Asp Pro Ser Leu Ser Glu Met Val Val Val Ala Ile Gln Ile Leu Arg 
    290                 295                 300                 


Lys Asn Pro Lys Gly Phe Phe Leu Leu Val Glu Gly Gly Arg Ile Asp 
305                 310                 315                 320 


His Gly His His Glu Gly Lys Ala Lys Gln Ala Leu His Glu Ala Val 
                325                 330                 335     


Glu Met Asp Arg Ala Ile Gly Gln Ala Gly Ser Leu Thr Ser Ser Glu 
            340                 345                 350         


Asp Thr Leu Thr Val Val Thr Ala Asp His Ser His Val Phe Thr Phe 
        355                 360                 365             


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


Leu Ser Asp Thr Asp Lys Lys Pro Phe Thr Ala Ile Leu Tyr Gly Asn 
385                 390                 395                 400 


Gly Pro Gly Tyr Lys Val Val Gly Gly Glu Arg Glu Asn Val Ser Met 
                405                 410                 415     


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


Arg His Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ser Lys Gly 
        435                 440                 445             


Pro Met Ala His Leu Leu His Gly Val His Glu Gln Asn Tyr Val Pro 
    450                 455                 460                 


His Val Met Ala Tyr Ala Ala Cys Ile Gly Ala Asn Leu Gly His Cys 
465                 470                 475                 480 


Ala Pro Ala Ser Ser 
                485 


<210> 3
<211> 227
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 3
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


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


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


<210> 4
<211> 726
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 4
Leu Val Pro Glu Lys Glu Lys Asp Pro Lys Tyr Trp Arg Asp Gln Ala 
1               5                   10                  15      


Gln Glu Thr Leu Lys Tyr Ala Leu Glu Leu Gln Lys Leu Asn Thr Asn 
            20                  25                  30          


Val Ala Lys Asn Val Ile Met Phe Leu Gly Asp Gly Met Gly Val Ser 
        35                  40                  45              


Thr Val Thr Ala Ala Arg Ile Leu Lys Gly Gln Leu His His Asn Pro 
    50                  55                  60                  


Gly Glu Glu Thr Arg Leu Glu Met Asp Lys Phe Pro Phe Val Ala Leu 
65                  70                  75                  80  


Ser Lys Thr Tyr Asn Thr Asn Ala Gln Val Pro Asp Ser Ala Gly Thr 
                85                  90                  95      


Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Glu Gly Thr Val Gly 
            100                 105                 110         


Val Ser Ala Ala Thr Glu Arg Ser Arg Cys Asn Thr Thr Gln Gly Asn 
        115                 120                 125             


Glu Val Thr Ser Ile Leu Arg Trp Ala Lys Asp Ala Gly Lys Ser Val 
    130                 135                 140                 


Gly Ile Val Thr Thr Thr Arg Val Asn His Ala Thr Pro Ser Ala Ala 
145                 150                 155                 160 


Tyr Ala His Ser Ala Asp Arg Asp Trp Tyr Ser Asp Asn Glu Met Pro 
                165                 170                 175     


Pro Glu Ala Leu Ser Gln Gly Cys Lys Asp Ile Ala Tyr Gln Leu Met 
            180                 185                 190         


His Asn Ile Arg Asp Ile Asp Val Ile Met Gly Gly Gly Arg Lys Tyr 
        195                 200                 205             


Met Tyr Pro Lys Asn Lys Thr Asp Val Glu Tyr Glu Ser Asp Glu Lys 
    210                 215                 220                 


Ala Arg Gly Thr Arg Leu Asp Gly Leu Asp Leu Val Asp Thr Trp Lys 
225                 230                 235                 240 


Ser Phe Lys Pro Arg Tyr Lys His Ser His Phe Ile Trp Asn Arg Thr 
                245                 250                 255     


Glu Leu Leu Thr Leu Asp Pro His Asn Val Asp Tyr Leu Leu Gly Leu 
            260                 265                 270         


Phe Glu Pro Gly Asp Met Gln Tyr Glu Leu Asn Arg Asn Asn Val Thr 
        275                 280                 285             


Asp Pro Ser Leu Ser Glu Met Val Val Val Ala Ile Gln Ile Leu Arg 
    290                 295                 300                 


Lys Asn Pro Lys Gly Phe Phe Leu Leu Val Glu Gly Gly Arg Ile Asp 
305                 310                 315                 320 


His Gly His His Glu Gly Lys Ala Lys Gln Ala Leu His Glu Ala Val 
                325                 330                 335     


Glu Met Asp Arg Ala Ile Gly Gln Ala Gly Ser Leu Thr Ser Ser Glu 
            340                 345                 350         


Asp Thr Leu Thr Val Val Thr Ala Asp His Ser His Val Phe Thr Phe 
        355                 360                 365             


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


Leu Ser Asp Thr Asp Lys Lys Pro Phe Thr Ala Ile Leu Tyr Gly Asn 
385                 390                 395                 400 


Gly Pro Gly Tyr Lys Val Val Gly Gly Glu Arg Glu Asn Val Ser Met 
                405                 410                 415     


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


Arg His Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ser Lys Gly 
        435                 440                 445             


Pro Met Ala His Leu Leu His Gly Val His Glu Gln Asn Tyr Val Pro 
    450                 455                 460                 


His Val Met Ala Tyr Ala Ala Cys Ile Gly Ala Asn Leu Gly His Cys 
465                 470                 475                 480 


Ala Pro Ala Ser Ser Leu Lys Asp Lys Thr His Thr Cys Pro Pro Cys 
                485                 490                 495     


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
            500                 505                 510         


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
        515                 520                 525             


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
    530                 535                 540                 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
545                 550                 555                 560 


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                565                 570                 575     


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
            580                 585                 590         


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
        595                 600                 605             


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
    610                 615                 620                 


Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
625                 630                 635                 640 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                645                 650                 655     


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
            660                 665                 670         


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
        675                 680                 685             


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
    690                 695                 700                 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Asp Ile Asp Asp Asp Asp 
705                 710                 715                 720 


Asp Asp Asp Asp Asp Asp 
                725     


