                         SEQUENCE LISTING

<110>  Protalix Ltd.
       CHEN ZELTSBURG, Lilach
       RUDERFER, Ilya
       SHULMAN, Avidor
       FUX, Liat
       UGORTSEV, Yulia
       NETA, Hagit
       GELLEY, Sivan
       LAVEE LAVIAD, Elad
       SHAALTIEL, Yoseph
 
<120>  MODIFIED DNASE AND USES THEREOF

<130>  64114

<150>  US 62/247,856
<151>  2015-10-29

<150>  US 62/169,724
<151>  2015-06-02

<150>  US 62/163,497
<151>  2015-05-19

<150>  US 62/099,565
<151>  2015-01-04

<150>  US 62/099,560
<151>  2015-01-04

<160>  9     

<170>  PatentIn version 3.5

<210>  1
<211>  260
<212>  PRT
<213>  Homo sapiens

<400>  1

Leu Lys Ile Ala Ala Phe Asn Ile Gln Thr Phe Gly Glu Thr Lys Met 
1               5                   10                  15      


Ser Asn Ala Thr Leu Val Ser Tyr Ile Val Gln Ile Leu Ser Arg Tyr 
            20                  25                  30          


Asp Ile Ala Leu Val Gln Glu Val Arg Asp Ser His Leu Thr Ala Val 
        35                  40                  45              


Gly Lys Leu Leu Asp Asn Leu Asn Gln Asp Ala Pro Asp Thr Tyr His 
    50                  55                  60                  


Tyr Val Val Ser Glu Pro Leu Gly Arg Asn Ser Tyr Lys Glu Arg Tyr 
65                  70                  75                  80  


Leu Phe Val Tyr Arg Pro Asp Gln Val Ser Ala Val Asp Ser Tyr Tyr 
                85                  90                  95      


Tyr Asp Asp Gly Cys Glu Pro Cys Gly Asn Asp Thr Phe Asn Arg Glu 
            100                 105                 110         


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


Ala Ile Val Pro Leu His Ala Ala Pro Gly Asp Ala Val Ala Glu Ile 
    130                 135                 140                 


Asp Ala Leu Tyr Asp Val Tyr Leu Asp Val Gln Glu Lys Trp Gly Leu 
145                 150                 155                 160 


Glu Asp Val Met Leu Met Gly Asp Phe Asn Ala Gly Cys Ser Tyr Val 
                165                 170                 175     


Arg Pro Ser Gln Trp Ser Ser Ile Arg Leu Trp Thr Ser Pro Thr Phe 
            180                 185                 190         


Gln Trp Leu Ile Pro Asp Ser Ala Asp Thr Thr Ala Thr Pro Thr His 
        195                 200                 205             


Cys Ala Tyr Asp Arg Ile Val Val Ala Gly Met Leu Leu Arg Gly Ala 
    210                 215                 220                 


Val Val Pro Asp Ser Ala Leu Pro Phe Asn Phe Gln Ala Ala Tyr Gly 
225                 230                 235                 240 


Leu Ser Asp Gln Leu Ala Gln Ala Ile Ser Asp His Tyr Pro Val Glu 
                245                 250                 255     


Val Met Leu Lys 
            260 


<210>  2
<211>  261
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Putative amino acid sequence of the purified, plant expressed 
       rhDNase I

<400>  2

Gly Leu Lys Ile Ala Ala Phe Asn Ile Gln Thr Phe Gly Glu Thr Lys 
1               5                   10                  15      


Met Ser Asn Ala Thr Leu Val Ser Tyr Ile Val Gln Ile Leu Ser Arg 
            20                  25                  30          


Tyr Asp Ile Ala Leu Val Gln Glu Val Arg Asp Ser His Leu Thr Ala 
        35                  40                  45              


Val Gly Lys Leu Leu Asp Asn Leu Asn Gln Asp Ala Pro Asp Thr Tyr 
    50                  55                  60                  


His Tyr Val Val Ser Glu Pro Leu Gly Arg Asn Ser Tyr Lys Glu Arg 
65                  70                  75                  80  


Tyr Leu Phe Val Tyr Arg Pro Asp Gln Val Ser Ala Val Asp Ser Tyr 
                85                  90                  95      


Tyr Tyr Asp Asp Gly Cys Glu Pro Cys Gly Asn Asp Thr Phe Asn Arg 
            100                 105                 110         


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


Phe Ala Ile Val Pro Leu His Ala Ala Pro Gly Asp Ala Val Ala Glu 
    130                 135                 140                 


Ile Asp Ala Leu Tyr Asp Val Tyr Leu Asp Val Gln Glu Lys Trp Gly 
145                 150                 155                 160 


Leu Glu Asp Val Met Leu Met Gly Asp Phe Asn Ala Gly Cys Ser Tyr 
                165                 170                 175     


Val Arg Pro Ser Gln Trp Ser Ser Ile Arg Leu Trp Thr Ser Pro Thr 
            180                 185                 190         


Phe Gln Trp Leu Ile Pro Asp Ser Ala Asp Thr Thr Ala Thr Pro Thr 
        195                 200                 205             


His Cys Ala Tyr Asp Arg Ile Val Val Ala Gly Met Leu Leu Arg Gly 
    210                 215                 220                 


Ala Val Val Pro Asp Ser Ala Leu Pro Phe Asn Phe Gln Ala Ala Tyr 
225                 230                 235                 240 


Gly Leu Ser Asp Gln Leu Ala Gln Ala Ile Ser Asp His Tyr Pro Val 
                245                 250                 255     


Glu Val Met Leu Lys 
            260     


<210>  3
<211>  99
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Coding sequence of polypeptide of ABPI leader signal

<400>  3
atgattgtgc tttctgtggg atctgcttct tcttctccaa ttgtggtggt gttctctgtg       60

gctcttcttc ttttctactt ctctgagact tctcttggc                              99


<210>  4
<211>  849
<212>  DNA
<213>  Homo sapiens

<400>  4
atgaggggca tgaagctgct gggggcgctg ctggcactgg cggccctact gcagggggcc       60

gtgtccctga agatcgcagc cttcaacatc cagacatttg gggagaccaa gatgtccaat      120

gccaccctcg tcagctacat tgtgcagatc ctgagccgct atgacatcgc cctggtccag      180

gaggtcagag acagccacct gactgccgtg gggaagctgc tggacaacct caatcaggat      240

gcaccagaca cctatcacta cgtggtcagt gagccactgg gacggaacag ctataaggag      300

cgctacctgt tcgtgtacag gcctgaccag gtgtctgcgg tggacagcta ctactacgat      360

gatggctgcg agccctgcgg gaacgacacc ttcaaccgag agccagccat tgtcaggttc      420

ttctcccggt tcacagaggt cagggagttt gccattgttc ccctgcatgc ggccccgggg      480

gacgcagtag ccgagatcga cgctctctat gacgtctacc tggatgtcca agagaaatgg      540

ggcttggagg acgtcatgtt gatgggcgac ttcaatgcgg gctgcagcta tgtgagaccc      600

tcccagtggt catccatccg cctgtggaca agccccacct tccagtggct gatccccgac      660

agcgctgaca ccacagctac acccacgcac tgtgcctatg acaggatcgt ggttgcaggg      720

atgctgctcc gaggcgccgt tgttcccgac tcggctcttc cctttaactt ccaggctgcc      780

tatggcctga gtgaccaact ggcccaagcc atcagtgacc actatccagt ggaggtgatg      840

ctgaagtga                                                              849


<210>  5
<211>  282
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Arg Gly Met Lys Leu Leu Gly Ala Leu Leu Ala Leu Ala Ala Leu 
1               5                   10                  15      


Leu Gln Gly Ala Val Ser Leu Lys Ile Ala Ala Phe Asn Ile Gln Thr 
            20                  25                  30          


Phe Gly Glu Thr Lys Met Ser Asn Ala Thr Leu Val Ser Tyr Ile Val 
        35                  40                  45              


Gln Ile Leu Ser Arg Tyr Asp Ile Ala Leu Val Gln Glu Val Arg Asp 
    50                  55                  60                  


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


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


Ser Tyr Lys Glu Arg Tyr Leu Phe Val Tyr Arg Pro Asp Gln Val Ser 
            100                 105                 110         


Ala Val Asp Ser Tyr Tyr Tyr Asp Asp Gly Cys Glu Pro Cys Gly Asn 
        115                 120                 125             


Asp Thr Phe Asn Arg Glu Pro Ala Ile Val Arg Phe Phe Ser Arg Phe 
    130                 135                 140                 


Thr Glu Val Arg Glu Phe Ala Ile Val Pro Leu His Ala Ala Pro Gly 
145                 150                 155                 160 


Asp Ala Val Ala Glu Ile Asp Ala Leu Tyr Asp Val Tyr Leu Asp Val 
                165                 170                 175     


Gln Glu Lys Trp Gly Leu Glu Asp Val Met Leu Met Gly Asp Phe Asn 
            180                 185                 190         


Ala Gly Cys Ser Tyr Val Arg Pro Ser Gln Trp Ser Ser Ile Arg Leu 
        195                 200                 205             


Trp Thr Ser Pro Thr Phe Gln Trp Leu Ile Pro Asp Ser Ala Asp Thr 
    210                 215                 220                 


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


Met Leu Leu Arg Gly Ala Val Val Pro Asp Ser Ala Leu Pro Phe Asn 
                245                 250                 255     


Phe Gln Ala Ala Tyr Gly Leu Ser Asp Gln Leu Ala Gln Ala Ile Ser 
            260                 265                 270         


Asp His Tyr Pro Val Glu Val Met Leu Lys 
        275                 280         


<210>  6
<211>  786
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Coding sequence of the recombinant DNase I without the leader 
       sequence

<400>  6
cttaaaatcg ctgctttcaa catccaaact ttcggagaga ctaagatgtc taacgctact       60

cttgtgtcct acatcgttca gattctctcc agatacgata ttgctcttgt tcaggaagtt      120

agggattctc accttactgc tgtgggaaag cttcttgata acctcaatca ggatgctcca      180

gatacttacc actacgttgt gtctgaacca cttggaagaa actcctacaa agagcgttac      240

ctctttgttt accgtccaga tcaagtttct gctgtggatt cctactacta cgatgatgga      300

tgtgagccat gcggaaacga tactttcaat agagagccag ctatcgttcg ttttttcagt      360

aggttcactg aagttcgtga gtttgctatt gtgccacttc atgctgctcc aggtgatgct      420

gttgctgaga ttgatgctct ctacgatgtg taccttgatg ttcaagagaa gtggggattg      480

gaggatgtta tgctcatggg agatttcaat gctggatgct cttatgttag gccatctcag      540

tggtcatcta ttaggctttg gacttcccca actttccaat ggcttatccc agattccgct      600

gatacaactg ctactccaac tcattgtgct tacgatagga ttgtggtggc tggaatgctt      660

cttagaggtg ctgttgttcc agattctgct ctcccattca atttccaagc tgcttacgga      720

ctttctgatc aacttgctca ggctatttct gatcactacc cagttgaggt gatgttgaag      780

tgatga                                                                 786


<210>  7
<211>  885
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Coding sequence of rhDNase I (ABPI+DNase I)

<400>  7
atgattgtgc tttctgtggg atctgcttct tcttctccaa ttgtggtggt gttctctgtg       60

gctcttcttc ttttctactt ctctgagact tctcttggcc ttaaaatcgc tgctttcaac      120

atccaaactt tcggagagac taagatgtct aacgctactc ttgtgtccta catcgttcag      180

attctctcca gatacgatat tgctcttgtt caggaagtta gggattctca ccttactgct      240

gtgggaaagc ttcttgataa cctcaatcag gatgctccag atacttacca ctacgttgtg      300

tctgaaccac ttggaagaaa ctcctacaaa gagcgttacc tctttgttta ccgtccagat      360

caagtttctg ctgtggattc ctactactac gatgatggat gtgagccatg cggaaacgat      420

actttcaata gagagccagc tatcgttcgt tttttcagta ggttcactga agttcgtgag      480

tttgctattg tgccacttca tgctgctcca ggtgatgctg ttgctgagat tgatgctctc      540

tacgatgtgt accttgatgt tcaagagaag tggggattgg aggatgttat gctcatggga      600

gatttcaatg ctggatgctc ttatgttagg ccatctcagt ggtcatctat taggctttgg      660

acttccccaa ctttccaatg gcttatccca gattccgctg atacaactgc tactccaact      720

cattgtgctt acgataggat tgtggtggct ggaatgcttc ttagaggtgc tgttgttcca      780

gattctgctc tcccattcaa tttccaagct gcttacggac tttctgatca acttgctcag      840

gctatttctg atcactaccc agttgaggtg atgttgaagt gatga                      885


<210>  8
<211>  33
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Arabidopsis derived ABPI endoplasmic reticulum targeting signal 
       peptide

<400>  8

Met Ile Val Leu Ser Val Gly Ser Ala Ser Ser Ser Pro Ile Val Val 
1               5                   10                  15      


Val Phe Ser Val Ala Leu Leu Leu Phe Tyr Phe Ser Glu Thr Ser Leu 
            20                  25                  30          


Gly 
    


<210>  9
<211>  293
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Plant recombinant human DNase I

<400>  9

Met Ile Val Leu Ser Val Gly Ser Ala Ser Ser Ser Pro Ile Val Val 
1               5                   10                  15      


Val Phe Ser Val Ala Leu Leu Leu Phe Tyr Phe Ser Glu Thr Ser Leu 
            20                  25                  30          


Gly Leu Lys Ile Ala Ala Phe Asn Ile Gln Thr Phe Gly Glu Thr Lys 
        35                  40                  45              


Met Ser Asn Ala Thr Leu Val Ser Tyr Ile Val Gln Ile Leu Ser Arg 
    50                  55                  60                  


Tyr Asp Ile Ala Leu Val Gln Glu Val Arg Asp Ser His Leu Thr Ala 
65                  70                  75                  80  


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


His Tyr Val Val Ser Glu Pro Leu Gly Arg Asn Ser Tyr Lys Glu Arg 
            100                 105                 110         


Tyr Leu Phe Val Tyr Arg Pro Asp Gln Val Ser Ala Val Asp Ser Tyr 
        115                 120                 125             


Tyr Tyr Asp Asp Gly Cys Glu Pro Cys Gly Asn Asp Thr Phe Asn Arg 
    130                 135                 140                 


Glu Pro Ala Ile Val Arg Phe Phe Ser Arg Phe Thr Glu Val Arg Glu 
145                 150                 155                 160 


Phe Ala Ile Val Pro Leu His Ala Ala Pro Gly Asp Ala Val Ala Glu 
                165                 170                 175     


Ile Asp Ala Leu Tyr Asp Val Tyr Leu Asp Val Gln Glu Lys Trp Gly 
            180                 185                 190         


Leu Glu Asp Val Met Leu Met Gly Asp Phe Asn Ala Gly Cys Ser Tyr 
        195                 200                 205             


Val Arg Pro Ser Gln Trp Ser Ser Ile Arg Leu Trp Thr Ser Pro Thr 
    210                 215                 220                 


Phe Gln Trp Leu Ile Pro Asp Ser Ala Asp Thr Thr Ala Thr Pro Thr 
225                 230                 235                 240 


His Cys Ala Tyr Asp Arg Ile Val Val Ala Gly Met Leu Leu Arg Gly 
                245                 250                 255     


Ala Val Val Pro Asp Ser Ala Leu Pro Phe Asn Phe Gln Ala Ala Tyr 
            260                 265                 270         


Gly Leu Ser Asp Gln Leu Ala Gln Ala Ile Ser Asp His Tyr Pro Val 
        275                 280                 285             


Glu Val Met Leu Lys 
    290             


