SEQUENCE LISTING

<110>  Prothena Therapeutics Limited
       Tarlochan Nijjar
       Philip Dolan
       Robin Barbour
 
<120>  Treatment And Prophylaxis Of Amyloidosis

<130>  E090 1070US.P1

<160>  21   

<170>  PatentIn version 3.5

<210>  1
<211>  16
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VL CDR1

<400>  1

Arg Ser Ser Gln Ser Leu Val His Ser Thr Gly Asn Thr Tyr Leu His 
1               5                   10                  15      


<210>  2
<211>  7
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VL CDR2

<400>  2

Lys Val Ser Asn Arg Phe Ser 
1               5           


<210>  3
<211>  9
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VL CDR3

<400>  3

Ser Gln Ser Thr His Val Pro Phe Thr 
1               5                   


<210>  4
<211>  10
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VH CDR1

<400>  4

Gly Phe Thr Phe Asn Thr Tyr Ala Met Tyr 
1               5                   10  


<210>  5
<211>  19
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VH CDR2

<400>  5

Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Ile Tyr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            

<210>  6
<211>  8
<212>  PRT
<213>  Mus musculus

<220>
<223>  2A4 VH CDR3

<400>  6

Pro Tyr Ser Asp Ser Phe Ala Tyr 
1               5               


<210>  7
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 light chain variable region version 1

<400>  7

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Thr Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Tyr Phe Thr Leu Lys Ile 
65                  70                  75                  80  


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


Thr His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  8
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 light chain variable region version 2

<400>  8

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Thr Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  


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


Thr His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  9
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 light chain variable region version 3

<400>  9

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Thr Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110   


<210>  10
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 heavy chain variable region version 1

<400>  10

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


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


Ala Met Tyr Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


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


Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Val Arg Pro Tyr Ser Asp Ser Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  11
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 heavy chain variable region version 2

<400>  11

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


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


Ala Met Tyr Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


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


Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Val Arg Pro Tyr Ser Asp Ser Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  12
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 heavy chain variable region version 3

<400>  12

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


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


Ala Met Tyr Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


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


Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Pro Tyr Ser Asp Ser Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  13
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 kappa light chain

<400>  13

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Thr Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  14
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 2A4 IgG1 heavy chain variant 2 (G1m3 allotype)

<400>  14

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


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


Ala Met Tyr Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Arg Ile Arg Ser Lys Ser Asn Asn Tyr Ala Ile Tyr Tyr Ala Asp 
    50                  55                  60                  


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


Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Ala Arg Pro Tyr Ser Asp Ser Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             


Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 


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


Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     


Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         


Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             


Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 


Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         


Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 


Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             


Lys 
    
 
<210>  15
<211>  660
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized antibody sequence containing murine and human residues 
       (Hu2A4 VH3VL3 hcg1,k cDNA sequence - light chain without signal 
       sequence)

<400>  15

gacgtggtga tgacccagtc ccctctgtcc ctgcctgtga cccctggcga gcctgcctcc        60

atctcctgcc ggtcctccca gtccctggtg cactccaccg gcaacaccta tctgcactgg       120

tatctgcaga agcctggcca gtctcctcag ctgctgatct acaaggtgtc caaccggttc       180

tccggcgtgc ctgaccggtt ctctggctcc ggctccggca ccgacttcac cctgaagatc       240

tcccgggtgg aggccgagga cgtgggcgtg tactactgct cccagtccac ccacgtgcct       300

ttcaccttcg gcggaggtac caaggtggag atcaaacgaa ctgtggctgc accatctgtc       360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg       420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa       480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc       540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa       600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgttag       660


<210>  16
<211>  726
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized antibody sequence containing murine and human residues 
       (Hu2A4 VH3VL3 hcg1,k cDNA sequence - light chain)

<400>  16

atggacatgc gggtgcccgc acagctgctg ggcctgctga tgctgtgggt gtccggctcc        60

tccggcgacg tggtgatgac ccagtcccct ctgtccctgc ctgtgacccc tggcgagcct       120

gcctccatct cctgccggtc ctcccagtcc ctggtgcact ccaccggcaa cacctatctg       180

cactggtatc tgcagaagcc tggccagtct cctcagctgc tgatctacaa ggtgtccaac       240

cggttctccg gcgtgcctga ccggttctct ggctccggct ccggcaccga cttcaccctg       300

aagatctccc gggtggaggc cgaggacgtg ggcgtgtact actgctccca gtccacccac       360

gtgcctttca ccttcggcgg aggcaccaag gtggagatca agcgaactgt ggctgcacca       420

tctgtcttca tcttcccgcc atctgatgag cagttgaaat ctggaactgc ctctgttgtg       480

tgcctgctga ataacttcta tcccagagag gccaaagtac agtggaaggt ggataacgcc       540

ctccaatcgg gtaactccca ggagagtgtc acagagcagg acagcaagga cagcacctac       600

agcctcagca gcaccctgac gctgagcaaa gcagactacg agaaacacaa agtctacgcc       660

tgcgaagtca cccatcaggg cctgagctcg cccgtcacaa agagcttcaa caggggagag       720

tgttag                                                                  726


<210>  17
<211>  1347
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized antibody sequence containing murine and human residues 
       (Hu2A4 VH3VL3 hcg1,k cDNA sequence - heavy chain without signal 
       sequence)

<400>  17

gaagtgcaat tggtcgagtc cggcggaggc ctggtgcagc ctggcggctc cctgagactg        60

tcctgcgccg cctccggctt caccttcaac acctacgcca tgtactggat caggcaggct       120

cctggcaagg gactggagtg ggtggcccgg atcaggtcca agtccaacaa ctacgctatc       180

tactacgccg actccgtgaa ggaccggttc accatctccc gggacgactc caagaactcc       240

ctgtatctgc agatgaactc cctgaaaacc gaggacaccg ccgtgtacta ctgcgctcgg       300

ccttactccg actccttcgc ctactggggc cagggcaccc tggtgaccgt gagctcagcc       360

tccaccaagg gtccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc       420

acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg       480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga       540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac       600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagagagt tgagcccaaa       660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg       720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag       780

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac       840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc       900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag       960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa      1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg      1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc      1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg      1200

gactccgacg gctccttctt cctctatagc aagctcaccg tggacaagag caggtggcag      1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag      1320

aagagcctct ccctgtcccc gggtaaa                                          1347


<210>  18
<211>  1404
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized antibody sequence containing murine and human residues 
       (Hu2A4 VH3VL3 hcg1,k cDNA sequence - heavy chain)

<400>  18

atggagttcg gcctgtcctg gctgttcctg gtggccatcc tgaagggcgt gcagtgcgaa        60

gtgcaattgg tcgagtccgg cggaggcctg gtgcagcctg gcggctccct gagactgtcc       120

tgcgccgcct ccggcttcac cttcaacacc tacgccatgt actggatcag gcaggctcct       180

ggcaagggac tggagtgggt ggcccggatc aggtccaagt ccaacaacta cgctatctac       240

tacgccgact ccgtgaagga ccggttcacc atctcccggg acgactccaa gaactccctg       300

tatctgcaga tgaactccct gaaaaccgag gacaccgccg tgtactactg cgctcggcct       360

tactccgact ccttcgccta ctggggccag ggcaccctgg tgaccgtgag ctcagcctcc       420

accaagggtc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca       480

gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac       540

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc       600

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc       660

tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agagagttga gcccaaatct       720

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca       780

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc       840

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg       900

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg       960

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac      1020

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc      1080

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga ggagatgacc      1140

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg      1200

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac      1260

tccgacggct ccttcttcct ctatagcaag ctcaccgtgg acaagagcag gtggcagcag      1320

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag      1380

agcctctccc tgtccccggg taaa                                             1404


<210>  19
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Immunoglobulin light chain sequence

<400>  19

His Glu Asp Thr 
1               


<210>  20
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Immunoglobulin light chain sequence

<400>  20

Ala Glu Asp Ser 
1              


<210>  21
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Immunoglobulin light chain sequence

<400>  21

His Gly Asp Thr
1               


