                         SEQUENCE LISTING

<110>  Yeda Research and Development Co. Ltd.
       SAGI, Irit
       AFRATIS, Nikolaos A.
 
<120>  COMPOSITIONS COMPRISING THE PROPEPTIDE OF LYSYL OXIDASE AND USES 
       THEREOF

<130>  82310

<150>  IL 266433
<151>  2019-05-02

<150>  US 62/977,792
<151>  2020-02-18

<160>  14    

<170>  PatentIn version 3.5

<210>  1
<211>  148
<212>  PRT
<213>  Artificial sequence

<220>
<223>  LOX  auto-inhibitory LPD amino acid sequence

<400>  1

Ala Pro Pro Ala Ala Gly Gln Gln Gln Pro Pro Arg Glu Pro Pro Ala 
1               5                   10                  15      


Ala Pro Gly Ala Trp Arg Gln Gln Ile Gln Trp Glu Asn Asn Gly Gln 
            20                  25                  30          


Val Phe Ser Leu Leu Ser Leu Gly Ser Gln Tyr Gln Pro Gln Arg Arg 
        35                  40                  45              


Arg Asp Pro Gly Ala Ala Val Pro Gly Ala Ala Asn Ala Ser Ala Gln 
    50                  55                  60                  


Gln Pro Arg Thr Pro Ile Leu Leu Ile Arg Asp Asn Arg Thr Ala Ala 
65                  70                  75                  80  


Ala Arg Thr Arg Thr Ala Gly Ser Ser Gly Val Thr Ala Gly Arg Pro 
                85                  90                  95      


Arg Pro Thr Ala Arg His Trp Phe Gln Ala Gly Tyr Ser Thr Ser Arg 
            100                 105                 110         


Ala Arg Glu Pro Gly Ala Ser Arg Ala Glu Asn Gln Thr Ala Pro Gly 
        115                 120                 125             


Glu Val Pro Ala Leu Ser Asn Leu Arg Pro Pro Ser Arg Val Asp Gly 
    130                 135                 140                 


Met Val Gly Asp 
145             


<210>  2
<211>  444
<212>  DNA
<213>  Artificial sequence

<220>
<223>  LOX  auto-inhibitory LPD nucleic acid sequence

<400>  2
gcgccgccgg cggctggtca gcagcagccg ccgcgtgaac caccggcggc accgggcgcc       60

tggcgccagc agatccagtg ggaaaacaac ggtcaggtgt tcagcctgct gtctctgggc      120

tctcagtatc agccgcagcg tcgtcgtgat ccgggcgcgg cagttccggg tgctgcgaac      180

gcttctgcgc agcagccgcg taccccgatt ctgctgatcc gtgacaatcg taccgctgca      240

gcccgtaccc gtactgcggg cagctccggc gttaccgctg gtcgtccgcg tcctaccgct      300

cgtcattggt ttcaggctgg ctactctacg tctcgtgcgc gtgaagcggg cgcatcccgc      360

gctgaaaacc agaccgctcc gggtgaagta ccggcgctga gcaacctgcg cccgccgagc      420

cgcgtggatg gcatggtggg cgac                                             444


<210>  3
<211>  417
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Full length LOX amino acid sequence

<400>  3

Met Arg Phe Ala Trp Thr Val Leu Leu Leu Gly Pro Leu Gln Leu Cys 
1               5                   10                  15      


Ala Leu Val His Cys Ala Pro Pro Ala Ala Gly Gln Gln Gln Pro Pro 
            20                  25                  30          


Arg Glu Pro Pro Ala Ala Pro Gly Ala Trp Arg Gln Gln Ile Gln Trp 
        35                  40                  45              


Glu Asn Asn Gly Gln Val Phe Ser Leu Leu Ser Leu Gly Ser Gln Tyr 
    50                  55                  60                  


Gln Pro Gln Arg Arg Arg Asp Pro Gly Ala Ala Val Pro Gly Ala Ala 
65                  70                  75                  80  


Asn Ala Ser Ala Gln Gln Pro Arg Thr Pro Ile Leu Leu Ile Arg Asp 
                85                  90                  95      


Asn Arg Thr Ala Ala Ala Arg Thr Arg Thr Ala Gly Ser Ser Gly Val 
            100                 105                 110         


Thr Ala Gly Arg Pro Arg Pro Thr Ala Arg His Trp Phe Gln Ala Gly 
        115                 120                 125             


Tyr Ser Thr Ser Arg Ala Arg Glu Ala Gly Ala Ser Arg Ala Glu Asn 
    130                 135                 140                 


Gln Thr Ala Pro Gly Glu Val Pro Ala Leu Ser Asn Leu Arg Pro Pro 
145                 150                 155                 160 


Ser Arg Val Asp Gly Met Val Gly Asp Asp Pro Tyr Asn Pro Tyr Lys 
                165                 170                 175     


Tyr Ser Asp Asp Asn Pro Tyr Tyr Asn Tyr Tyr Asp Thr Tyr Glu Arg 
            180                 185                 190         


Pro Arg Pro Gly Gly Arg Tyr Arg Pro Gly Tyr Gly Thr Gly Tyr Phe 
        195                 200                 205             


Gln Tyr Gly Leu Pro Asp Leu Val Ala Asp Pro Tyr Tyr Ile Gln Ala 
    210                 215                 220                 


Ser Thr Tyr Val Gln Lys Met Ser Met Tyr Asn Leu Arg Cys Ala Ala 
225                 230                 235                 240 


Glu Glu Asn Cys Leu Ala Ser Thr Ala Tyr Arg Ala Asp Val Arg Asp 
                245                 250                 255     


Tyr Asp His Arg Val Leu Leu Arg Phe Pro Gln Arg Val Lys Asn Gln 
            260                 265                 270         


Gly Thr Ser Asp Phe Leu Pro Ser Arg Pro Arg Tyr Ser Trp Glu Trp 
        275                 280                 285             


His Ser Cys His Gln His Tyr His Ser Met Asp Glu Phe Ser His Tyr 
    290                 295                 300                 


Asp Leu Leu Asp Ala Asn Thr Gln Arg Arg Val Ala Glu Gly His Lys 
305                 310                 315                 320 


Ala Ser Phe Cys Leu Glu Asp Thr Ser Cys Asp Tyr Gly Tyr His Arg 
                325                 330                 335     


Arg Phe Ala Cys Thr Ala His Thr Gln Gly Leu Ser Pro Gly Cys Tyr 
            340                 345                 350         


Asp Thr Tyr Gly Ala Asp Ile Asp Cys Gln Trp Ile Asp Ile Thr Asp 
        355                 360                 365             


Val Lys Pro Gly Asn Tyr Ile Leu Lys Val Ser Val Asn Pro Ser Tyr 
    370                 375                 380                 


Leu Val Pro Glu Ser Asp Tyr Thr Asn Asn Val Val Arg Cys Asp Ile 
385                 390                 395                 400 


Arg Tyr Thr Gly His His Ala Tyr Ala Ser Gly Cys Thr Ile Ser Pro 
                405                 410                 415     


Tyr 
    


<210>  4
<211>  1251
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Full length LOX nucleic acid sequence

<400>  4
atgcgcttcg cctggaccgt gctcctgctc gggcctttgc agctctgcgc gctagtgcac       60

tgcgcgccgc cggcggctgg tcagcagcag ccgccgcgtg aaccaccggc ggcaccgggc      120

gcctggcgcc agcagatcca gtgggaaaac aacggtcagg tgttcagcct gctgtctctg      180

ggctctcagt atcagccgca gcgtcgtcgt gatccgggcg cggcagttcc gggtgctgcg      240

aacgcttctg cgcagcagcc gcgtaccccg attctgctga tccgtgacaa tcgtaccgct      300

gcagcccgta cccgtactgc gggcagctcc ggcgttaccg ctggtcgtcc gcgtcctacc      360

gctcgtcatt ggtttcaggc tggctactct acgtctcgtg cgcgtgaagc gggcgcatcc      420

cgcgctgaaa accagaccgc tccgggtgaa gtaccggcgc tgagcaacct gcgcccgccg      480

agccgcgtgg atggcatggt gggcgacgat ccatacaatc cgtacaaata ttctgatgac      540

aacccgtatt acaactatta cgatacttac gaacgcccac gccctggtgg ccgttaccgt      600

ccgggttacg gcaccggtta cttccagtac ggcctgccgg atctggtggc ggacccgtat      660

tatatccagg cgtccactta cgttcagaaa atgtctatgt acaacctgcg ttgcgcggca      720

gaagaaaact gcctggccag tacggcgtat cgcgccgacg tgcgtgacta cgaccaccgc      780

gtgttactgc gtttcccaca gcgtgttaaa aaccagggta ccagcgattt cctgccgtct      840

cgtccgcgct actcctggga atggcatagc tgccaccagc actatcattc catggacgaa      900

ttttcccatt atgacctgct ggatgcaaac acccagcgcc gcgtcgcaga aggccacaaa      960

gcgtcctttt gcctggaaga cacctcctgc gattacggct accaccgccg ttttgcgtgc     1020

accgcgcaca cccagggcct gtccccgggc tgctacgaca cctacggcgc cgacatcgac     1080

tgccagtgga tcgatatcac cgatgttaaa ccgggcaact atatcctgaa agttagcgtg     1140

aacccgagct acctggtgcc ggaaagcgat tacaccaaca acgtggttcg ttgcgacatc     1200

cgttacaccg gtcaccacgc gtatgcgtct ggttgcacca tttctccgta c              1251


<210>  5
<211>  413
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Exemplary amino acid sequence of a LPD fused to an Fc domain

<400>  5

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
        35                  40                  45              


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
    50                  55                  60                  


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
65                  70                  75                  80  


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
            100                 105                 110         


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
        115                 120                 125             


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
    130                 135                 140                 


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


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
                165                 170                 175     


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
            180                 185                 190         


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
        195                 200                 205             


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
    210                 215                 220                 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
225                 230                 235                 240 


Ser Leu Ser Leu Ser Pro Gly Lys Ala Ser Gly Ala Gly Ser Thr Thr 
                245                 250                 255     


Glu Asn Leu Tyr Phe Gln Gly Gly Ser Ala Pro Pro Ala Ala Gly Gln 
            260                 265                 270         


Gln Gln Pro Pro Arg Glu Pro Pro Ala Ala Pro Gly Ala Trp Arg Gln 
        275                 280                 285             


Gln Ile Gln Trp Glu Asn Asn Gly Gln Val Phe Ser Leu Leu Ser Leu 
    290                 295                 300                 


Gly Ser Gln Tyr Gln Pro Gln Arg Arg Arg Asp Pro Gly Ala Ala Val 
305                 310                 315                 320 


Pro Gly Ala Ala Asn Ala Ser Ala Gln Gln Pro Arg Thr Pro Ile Leu 
                325                 330                 335     


Leu Ile Arg Asp Asn Arg Thr Ala Ala Ala Arg Thr Arg Thr Ala Gly 
            340                 345                 350         


Ser Ser Gly Val Thr Ala Gly Arg Pro Arg Pro Thr Ala Arg His Trp 
        355                 360                 365             


Phe Gln Ala Gly Tyr Ser Thr Ser Arg Ala Arg Glu Ala Gly Ala Ser 
    370                 375                 380                 


Arg Ala Glu Asn Gln Thr Ala Pro Gly Glu Val Pro Ala Leu Ser Asn 
385                 390                 395                 400 


Leu Arg Pro Pro Ser Arg Val Asp Gly Met Val Gly Asp 
                405                 410             


<210>  6
<211>  1239
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Exemplary nucleic acid sequence of a LPD fused to an Fc domain

<400>  6
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggc       60

gccggatcaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca      120

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc      180

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg      240

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg      300

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac      360

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc      420

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc      480

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg      540

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac      600

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag      660

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag      720

agcctctccc tgtctcccgg gaaagctagc ggagccggaa gcacaaccga aaacctgtat      780

tttcagggcg gatccgcgcc gccggcggct ggtcagcagc agccgccgcg tgaaccaccg      840

gcggcaccgg gcgcctggcg ccagcagatc cagtgggaaa acaacggtca ggtgttcagc      900

ctgctgtctc tgggctctca gtatcagccg cagcgtcgtc gtgatccggg cgcggcagtt      960

ccgggtgctg cgaacgcttc tgcgcagcag ccgcgtaccc cgattctgct gatccgtgac     1020

aatcgtaccg ctgcagcccg tacccgtact gcgggcagct ccggcgttac cgctggtcgt     1080

ccgcgtccta ccgctcgtca ttggtttcag gctggctact ctacgtctcg tgcgcgtgaa     1140

gcgggcgcat cccgcgctga aaaccagacc gctccgggtg aagtaccggc gctgagcaac     1200

ctgcgcccgc cgagccgcgt ggatggcatg gtgggcgac                            1239


<210>  7
<211>  271
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Fc tag amino acid sequence

<400>  7

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
        35                  40                  45              


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
    50                  55                  60                  


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
65                  70                  75                  80  


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
            100                 105                 110         


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
        115                 120                 125             


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
    130                 135                 140                 


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


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
                165                 170                 175     


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
            180                 185                 190         


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
        195                 200                 205             


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
    210                 215                 220                 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
225                 230                 235                 240 


Ser Leu Ser Leu Ser Pro Gly Lys Ala Ser Gly Ala Gly Ser Thr Thr 
                245                 250                 255     


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


<210>  8
<211>  795
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Fc tag nucleic acid sequence

<400>  8
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggc       60

gccggatcaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca      120

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc      180

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg      240

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg      300

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac      360

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc      420

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc      480

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg      540

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac      600

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag      660

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag      720

agcctctccc tgtctcccgg gaaagctagc ggagccggaa gcacaaccga aaacctgtat      780

tttcagggcg gatcc                                                       795


<210>  9
<211>  248
<212>  PRT
<213>  Artificial sequence

<220>
<223>  LOX catalytic activity domain amino acid sequence

<400>  9

Asp Pro Tyr Asn Pro Tyr Lys Tyr Ser Asp Asp Asn Pro Tyr Tyr Asn 
1               5                   10                  15      


Tyr Tyr Asp Thr Tyr Glu Arg Pro Arg Pro Gly Gly Arg Tyr Arg Pro 
            20                  25                  30          


Gly Tyr Gly Thr Gly Tyr Phe Gln Tyr Gly Leu Pro Asp Leu Val Ala 
        35                  40                  45              


Asp Pro Tyr Tyr Ile Gln Ala Ser Thr Tyr Val Gln Lys Met Ser Met 
    50                  55                  60                  


Tyr Asn Leu Arg Cys Ala Ala Glu Glu Asn Cys Leu Ala Ser Thr Ala 
65                  70                  75                  80  


Tyr Arg Ala Asp Val Arg Asp Tyr Asp His Arg Val Leu Leu Arg Phe 
                85                  90                  95      


Pro Gln Arg Val Lys Asn Gln Gly Thr Ser Asp Phe Leu Pro Ser Arg 
            100                 105                 110         


Pro Arg Tyr Ser Trp Glu Trp His Ser Cys His Gln His Tyr His Ser 
        115                 120                 125             


Met Asp Glu Phe Ser His Tyr Asp Leu Leu Asp Ala Asn Thr Gln Arg 
    130                 135                 140                 


Arg Val Ala Glu Gly His Lys Ala Ser Phe Cys Leu Glu Asp Thr Ser 
145                 150                 155                 160 


Cys Asp Tyr Gly Tyr His Arg Arg Phe Ala Cys Thr Ala His Thr Gln 
                165                 170                 175     


Gly Leu Ser Pro Gly Cys Tyr Asp Thr Tyr Gly Ala Asp Ile Asp Cys 
            180                 185                 190         


Gln Trp Ile Asp Ile Thr Asp Val Lys Pro Gly Asn Tyr Ile Leu Lys 
        195                 200                 205             


Val Ser Val Asn Pro Ser Tyr Leu Val Pro Glu Ser Asp Tyr Thr Asn 
    210                 215                 220                 


Asn Val Val Arg Cys Asp Ile Arg Tyr Thr Gly His His Ala Tyr Ala 
225                 230                 235                 240 


Ser Gly Cys Thr Ile Ser Pro Tyr 
                245             


<210>  10
<211>  744
<212>  DNA
<213>  Artificial sequence

<220>
<223>  LOX catalytic activity domain nucleic acid sequence

<400>  10
gatccataca atccgtacaa atattctgat gacaacccgt attacaacta ttacgatact       60

tacgaacgcc cacgccctgg tggccgttac cgtccgggtt acggcaccgg ttacttccag      120

tacggcctgc cggatctggt ggcggacccg tattatatcc aggcgtccac ttacgttcag      180

aaaatgtcta tgtacaacct gcgttgcgcg gcagaagaaa actgcctggc cagtacggcg      240

tatcgcgccg acgtgcgtga ctacgaccac cgcgtgttac tgcgtttccc acagcgtgtt      300

aaaaaccagg gtaccagcga tttcctgccg tctcgtccgc gctactcctg ggaatggcat      360

agctgccacc agcactatca ttccatggac gaattttccc attatgacct gctggatgca      420

aacacccagc gccgcgtcgc agaaggccac aaagcgtcct tttgcctgga agacacctcc      480

tgcgattacg gctaccaccg ccgttttgcg tgcaccgcgc acacccaggg cctgtccccg      540

ggctgctacg acacctacgg cgccgacatc gactgccagt ggatcgatat caccgatgtt      600

aaaccgggca actatatcct gaaagttagc gtgaacccga gctacctggt gccggaaagc      660

gattacacca acaacgtggt tcgttgcgac atccgttaca ccggtcacca cgcgtatgcg      720

tctggttgca ccatttctcc gtac                                             744


<210>  11
<211>  148
<212>  PRT
<213>  Artificial sequence

<220>
<223>  mutated LPD amino acid sequence (N346, 362, 409Q)

<400>  11

Ala Pro Pro Ala Ala Gly Gln Gln Gln Pro Pro Arg Glu Pro Pro Ala 
1               5                   10                  15      


Ala Pro Gly Ala Trp Arg Gln Gln Ile Gln Trp Glu Asn Asn Gly Gln 
            20                  25                  30          


Val Phe Ser Leu Leu Ser Leu Gly Ser Gln Tyr Gln Pro Gln Arg Arg 
        35                  40                  45              


Arg Asp Pro Gly Ala Ala Val Pro Gly Ala Ala Gln Ala Ser Ala Gln 
    50                  55                  60                  


Gln Pro Arg Thr Pro Ile Leu Leu Ile Arg Asp Gln Arg Thr Ala Ala 
65                  70                  75                  80  


Ala Arg Thr Arg Thr Ala Gly Ser Ser Gly Val Thr Ala Gly Arg Pro 
                85                  90                  95      


Arg Pro Thr Ala Arg His Trp Phe Gln Ala Gly Tyr Ser Thr Ser Arg 
            100                 105                 110         


Ala Arg Glu Ala Gly Ala Ser Arg Ala Glu Gln Gln Thr Ala Pro Gly 
        115                 120                 125             


Glu Val Pro Ala Leu Ser Asn Leu Arg Pro Pro Ser Arg Val Asp Gly 
    130                 135                 140                 


Met Val Gly Asp 
145             


<210>  12
<211>  444
<212>  DNA
<213>  Artificial sequence

<220>
<223>  mutated LPD nucleic acid sequence (N346, 362, 409Q)

<400>  12
gcgccgccgg cggctggtca gcagcagccg ccgcgtgaac caccggcggc accgggcgcc       60

tggcgccagc agatccagtg ggaaaacaac ggtcaggtgt tcagcctgct gtctctgggc      120

tctcagtatc agccgcagcg tcgtcgtgat ccgggcgcgg cagttccggg tgctgcgcag      180

gcttctgcgc agcagccgcg taccccgatt ctgctgatcc gtgaccagcg taccgctgca      240

gcccgtaccc gtactgcggg cagctccggc gttaccgctg gtcgtccgcg tcctaccgct      300

cgtcattggt ttcaggctgg ctactctacg tctcgtgcgc gtgaagcggg cgcatcccgc      360

gctgaacagc agaccgctcc gggtgaagta ccggcgctga gcaacctgcg cccgccgagc      420

cgcgtggatg gcatggtggg cgac                                             444


<210>  13
<211>  413
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Fc-mutated LPD amino acid sequence

<400>  13

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
        35                  40                  45              


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
    50                  55                  60                  


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
65                  70                  75                  80  


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
            100                 105                 110         


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
        115                 120                 125             


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
    130                 135                 140                 


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


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
                165                 170                 175     


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
            180                 185                 190         


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
        195                 200                 205             


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
    210                 215                 220                 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
225                 230                 235                 240 


Ser Leu Ser Leu Ser Pro Gly Lys Ala Ser Gly Ala Gly Ser Thr Thr 
                245                 250                 255     


Glu Asn Leu Tyr Phe Gln Gly Gly Ser Ala Pro Pro Ala Ala Gly Gln 
            260                 265                 270         


Gln Gln Pro Pro Arg Glu Pro Pro Ala Ala Pro Gly Ala Trp Arg Gln 
        275                 280                 285             


Gln Ile Gln Trp Glu Asn Asn Gly Gln Val Phe Ser Leu Leu Ser Leu 
    290                 295                 300                 


Gly Ser Gln Tyr Gln Pro Gln Arg Arg Arg Asp Pro Gly Ala Ala Val 
305                 310                 315                 320 


Pro Gly Ala Ala Gln Ala Ser Ala Gln Gln Pro Arg Thr Pro Ile Leu 
                325                 330                 335     


Leu Ile Arg Asp Gln Arg Thr Ala Ala Ala Arg Thr Arg Thr Ala Gly 
            340                 345                 350         


Ser Ser Gly Val Thr Ala Gly Arg Pro Arg Pro Thr Ala Arg His Trp 
        355                 360                 365             


Phe Gln Ala Gly Tyr Ser Thr Ser Arg Ala Arg Glu Ala Gly Ala Ser 
    370                 375                 380                 


Arg Ala Glu Gln Gln Thr Ala Pro Gly Glu Val Pro Ala Leu Ser Asn 
385                 390                 395                 400 


Leu Arg Pro Pro Ser Arg Val Asp Gly Met Val Gly Asp 
                405                 410             


<210>  14
<211>  1239
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Fc-mutated LPD nucleic acid sequence

<400>  14
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggc       60

gccggatcaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca      120

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc      180

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg      240

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg      300

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac      360

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc      420

aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc      480

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg      540

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac      600

tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag      660

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag      720

agcctctccc tgtctcccgg gaaagctagc ggagccggaa gcacaaccga aaacctgtat      780

tttcagggcg gatccgcgcc gccggcggct ggtcagcagc agccgccgcg tgaaccaccg      840

gcggcaccgg gcgcctggcg ccagcagatc cagtgggaaa acaacggtca ggtgttcagc      900

ctgctgtctc tgggctctca gtatcagccg cagcgtcgtc gtgatccggg cgcggcagtt      960

ccgggtgctg cgcaggcttc tgcgcagcag ccgcgtaccc cgattctgct gatccgtgac     1020

cagcgtaccg ctgcagcccg tacccgtact gcgggcagct ccggcgttac cgctggtcgt     1080

ccgcgtccta ccgctcgtca ttggtttcag gctggctact ctacgtctcg tgcgcgtgaa     1140

gcgggcgcat cccgcgctga acagcagacc gctccgggtg aagtaccggc gctgagcaac     1200

ctgcgcccgc cgagccgcgt ggatggcatg gtgggcgac                            1239


