                         SEQUENCE LISTING

<110>  Biond Biologics LTD.
 
<120>  USE OF MMP-2 INHIBITION

<130>  BDB-P-009-PCT

<150>  US 62/942,240
<151>  2019-12-02

<150>  US 62/954802
<151>  2019-12-30

<150>  PCT/IL2020/050297
<151>  2020-03-12

<160>  31    

<170>  PatentIn version 3.5

<210>  1
<211>  220
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Leu Arg Leu Leu Leu Ala Leu Asn Leu Phe Pro Ser Ile Gln Val 
1               5                   10                  15      


Thr Gly Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr 
            20                  25                  30          


Asp Asn Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser 
        35                  40                  45              


Arg Glu Phe Arg Ala Ser Leu His Lys Gly Leu Asp Ser Ala Val Glu 
    50                  55                  60                  


Val Cys Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser 
65                  70                  75                  80  


Lys Thr Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr 
                85                  90                  95      


Phe Tyr Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys 
            100                 105                 110         


Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser 
        115                 120                 125             


Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
    130                 135                 140                 


Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly 
145                 150                 155                 160 


Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile 
                165                 170                 175     


Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met 
            180                 185                 190         


Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro 
        195                 200                 205             


Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
    210                 215                 220 


<210>  2
<211>  202
<212>  PRT
<213>  Homo sapiens

<400>  2

Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr Asp Asn 
1               5                   10                  15      


Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser Arg Glu 
            20                  25                  30          


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


Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser Lys Thr 
    50                  55                  60                  


Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr Phe Tyr 
65                  70                  75                  80  


Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys Lys Ile 
                85                  90                  95      


Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly 
            100                 105                 110         


Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe 
        115                 120                 125             


Pro Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly Val 
    130                 135                 140                 


Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp 
145                 150                 155                 160 


Val Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met 
                165                 170                 175     


Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala 
            180                 185                 190         


Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser 
        195                 200         


<210>  3
<211>  663
<212>  DNA
<213>  Homo sapiens

<400>  3
atgctcaggc tgctcttggc tctcaactta ttcccttcaa ttcaagtaac aggaaacaag       60

attttggtga agcagtcgcc catgcttgta gcgtacgaca atgcggtcaa ccttagctgc      120

aagtattcct acaatctctt ctcaagggag ttccgggcat cccttcacaa aggactggat      180

agtgctgtgg aagtctgtgt tgtatatggg aattactccc agcagcttca ggtttactca      240

aaaacggggt tcaactgtga tgggaaattg ggcaatgaat cagtgacatt ctacctccag      300

aatttgtatg ttaaccaaac agatatttac ttctgcaaaa ttgaagttat gtatcctcct      360

ccttacctag acaatgagaa gagcaatgga accattatcc atgtgaaagg gaaacacctt      420

tgtccaagtc ccctatttcc cggaccttct aagccctttt gggtgctggt ggtggttggt      480

ggagtcctgg cttgctatag cttgctagta acagtggcct ttattatttt ctgggtgagg      540

agtaagagga gcaggctcct gcacagtgac tacatgaaca tgactccccg ccgccccggg      600

cccacccgca agcattacca gccctatgcc ccaccacgcg acttcgcagc ctatcgctcc      660

tga                                                                    663


<210>  4
<211>  27
<212>  PRT
<213>  Homo sapiens

<400>  4

Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 
1               5                   10                  15      


Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 
            20                  25          


<210>  5
<211>  144
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Leu Arg Leu Leu Leu Ala Leu Asn Leu Phe Pro Ser Ile Gln Val 
1               5                   10                  15      


Thr Gly Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr 
            20                  25                  30          


Asp Asn Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser 
        35                  40                  45              


Arg Glu Phe Arg Ala Ser Leu His Lys Gly Leu Asp Ser Ala Val Glu 
    50                  55                  60                  


Val Cys Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser 
65                  70                  75                  80  


Lys Thr Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr 
                85                  90                  95      


Phe Tyr Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys 
            100                 105                 110         


Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser 
        115                 120                 125             


Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
    130                 135                 140                 


<210>  6
<211>  126
<212>  PRT
<213>  Homo sapiens

<400>  6

Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr Asp Asn 
1               5                   10                  15      


Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser Arg Glu 
            20                  25                  30          


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


Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser Lys Thr 
    50                  55                  60                  


Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr Phe Tyr 
65                  70                  75                  80  


Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys Lys Ile 
                85                  90                  95      


Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly 
            100                 105                 110         


Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro 
        115                 120                 125     


<210>  7
<211>  16
<212>  PRT
<213>  Homo sapiens

<400>  7

Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro 
1               5                   10                  15      


<210>  8
<211>  15
<212>  PRT
<213>  Homo sapiens

<400>  8

Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser 
1               5                   10                  15  


<210>  9
<211>  17
<212>  PRT
<213>  Homo sapiens

<400>  9

Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys 
1               5                   10                  15      


Pro 
    


<210>  10
<211>  19
<212>  PRT
<213>  Homo sapiens

<400>  10

His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro 
1               5                   10                  15      


Ser Lys Pro 
            


<210>  11
<211>  134
<212>  PRT
<213>  Homo sapiens

<400>  11

Asn Lys Ile Leu Val Lys Gln Ser Pro Met Leu Val Ala Tyr Asp Asn 
1               5                   10                  15      


Ala Val Asn Leu Ser Cys Lys Tyr Ser Tyr Asn Leu Phe Ser Arg Glu 
            20                  25                  30          


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


Val Val Tyr Gly Asn Tyr Ser Gln Gln Leu Gln Val Tyr Ser Lys Thr 
    50                  55                  60                  


Gly Phe Asn Cys Asp Gly Lys Leu Gly Asn Glu Ser Val Thr Phe Tyr 
65                  70                  75                  80  


Leu Gln Asn Leu Tyr Val Asn Gln Thr Asp Ile Tyr Phe Cys Lys Ile 
                85                  90                  95      


Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly 
            100                 105                 110         


Thr Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe 
        115                 120                 125             


Pro Gly Pro Ser Lys Pro 
    130                 


<210>  12
<211>  9
<212>  PRT
<213>  Homo sapiens

<400>  12

Lys Gly Lys His Leu Ser Pro Ser Pro 
1               5                   


<210>  13
<211>  9
<212>  PRT
<213>  Homo sapiens

<400>  13

Leu Phe Pro Gly Pro Ser Lys Pro Glu 
1               5                   


<210>  14
<211>  4
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic


<220>
<221>  X1
<222>  (2)..(2)
<223>  X1 is any amino acid

<220>
<221>  X2
<222>  (3)..(3)
<223>  X2 is any amino acid

<220>
<221>  X3
<222>  (4)..(4)
<223>  X3 is any hydrophobic amino acid

<400>  14

Pro Xaa Xaa Xaa 
1               


<210>  15
<211>  4
<212>  PRT
<213>  Homo sapiens

<400>  15

Pro Ser Pro Leu 
1               


<210>  16
<211>  18
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  16

Lys Gly Lys His Leu Ser Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys 
1               5                   10                  15      


Pro Glu 
        


<210>  17
<211>  33
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  17

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Gly Gly Gly His Val 
1               5                   10                  15      


Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys 
            20                  25                  30          


Pro 
    


<210>  18
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  18

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  19
<211>  33
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  19

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Gly Gly Gly His Val 
1               5                   10                  15      


Lys Gly Lys His Leu Cys Pro Ser Pro Lys Phe Pro Gly Pro Ser Lys 
            20                  25                  30          


Pro 
    


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

<220>
<223>  Synthetic

<400>  20

Pro Ser Pro Lys 
1               


<210>  21
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  21

Ile Asn Ala Met Gly 
1               5   


<210>  22
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  22

Ala Ile Ser Gly Gly Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys Gly 
1               5                   10                  15      


<210>  23
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  23

Asp Leu Tyr Gly Ser Asp Tyr Trp Asp 
1               5                   


<210>  24
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  24

Ile Asn Ala Met Ala 
1               5   


<210>  25
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  25

Ala Ile Thr Ser Ser Gly Ser Thr Asn Tyr Ala Asn Ser Val Lys Gly 
1               5                   10                  15      


<210>  26
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  26

Asp Glu Tyr Gly Ser Asp Tyr Trp Ile 
1               5                   


<210>  27
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  27

Ala Ile Thr Ser Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys Gly 
1               5                   10                  15      


<210>  28
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  28

Asp Leu Tyr Gly Glu Asp Tyr Trp Ile 
1               5                   


<210>  29
<211>  126
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  29

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Ile Ala Ser Ile Asn 
            20                  25                  30          


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


Ala Ala Ile Ser Gly Gly Gly Asp Thr Tyr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Val 
                85                  90                  95      


Val Asp Leu Tyr Gly Ser Asp Tyr Trp Asp Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ser Ala Ala Ala His His His His His His 
        115                 120                 125     


<210>  30
<211>  126
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  30

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Leu Phe Ser Ile Asn 
            20                  25                  30          


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


Ala Ala Ile Thr Ser Ser Gly Ser Thr Asn Tyr Ala Asn Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr Leu 
65                  70                  75                  80  


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


Val Asp Glu Tyr Gly Ser Asp Tyr Trp Ile Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ser Ala Ala Ala His His His His His His 
        115                 120                 125     


<210>  31
<211>  126
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  31

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Ile Phe Ser Ile Asn 
            20                  25                  30          


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


Ala Ala Ile Thr Ser Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


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


Gln Met Asn Asn Leu Glu Pro Arg Asp Ala Gly Val Tyr Tyr Cys Val 
                85                  90                  95      


Val Asp Leu Tyr Gly Glu Asp Tyr Trp Ile Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ser Ala Ala Ala His His His His His His 
        115                 120                 125     


