                               SEQUENCE LISTING

<110> TRUSTEES OF BOSTON UNIVERSITY
      BETH ISRAEL DEACONESS MEDICAL CENTER
 
<120> METHODS AND COMPOSITIONS FOR TREATING A FIBROTIC DISEASE

<130> 701586-097700WOPT

<140> PCT/US2021/033606
<141> 2021-05-21

<150> 63/028,961
<151> 2020-05-22

<160> 16    

<170> PatentIn version 3.5

<210> 1
<211> 185
<212> PRT
<213> Homo sapiens

<400> 1
Met Pro Arg Leu Phe Phe Phe His Leu Leu Gly Val Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Asp Ser Trp Met Glu Glu Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


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


Thr Glu Thr Ile Asn Met Met Ser Glu Phe Val Ala Asn Leu Pro Gln 
                85                  90                  95      


Glu Leu Lys Leu Thr Leu Ser Glu Met Gln Pro Ala Leu Pro Gln Leu 
            100                 105                 110         


Gln Gln His Val Pro Val Leu Lys Asp Ser Ser Leu Leu Phe Glu Glu 
        115                 120                 125             


Phe Lys Lys Leu Ile Arg Asn Arg Gln Ser Glu Ala Ala Asp Ser Ser 
    130                 135                 140                 


Pro Ser Glu Leu Lys Tyr Leu Gly Leu Asp Thr His Ser Arg Lys Lys 
145                 150                 155                 160 


Arg Gln Leu Tyr Ser Ala Leu Ala Asn Lys Cys Cys His Val Gly Cys 
                165                 170                 175     


Thr Lys Arg Ser Leu Ala Arg Phe Cys 
            180                 185 


<210> 2
<211> 185
<212> PRT
<213> Homo sapiens

<400> 2
Met Pro Arg Leu Phe Phe Phe His Leu Leu Gly Val Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Asp Ser Trp Met Glu Glu Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


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


Ile Glu Thr Ile Asn Met Met Ser Glu Phe Val Ala Asn Leu Pro Gln 
                85                  90                  95      


Glu Leu Lys Leu Ile Leu Ser Glu Met Gln Pro Ala Leu Pro Gln Leu 
            100                 105                 110         


Gln Gln His Val Pro Val Leu Lys Asp Ser Ser Leu Leu Phe Glu Glu 
        115                 120                 125             


Phe Lys Lys Leu Ile Arg Asn Arg Gln Ser Glu Ala Ala Asp Ser Ser 
    130                 135                 140                 


Pro Ser Glu Leu Lys Tyr Leu Gly Leu Asp Thr His Ser Arg Lys Lys 
145                 150                 155                 160 


Arg Gln Leu Tyr Ser Ala Leu Ala Asn Lys Cys Cys His Val Gly Cys 
                165                 170                 175     


Thr Lys Arg Ser Leu Ala Arg Phe Cys 
            180                 185 


<210> 3
<211> 185
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 3
Met Pro Arg Leu Phe Phe Phe His Leu Leu Gly Val Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Asp Ser Trp Met Glu Glu Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


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


Ile Glu Thr Ile Asn Met Met Ser Glu Phe Val Ala Asn Leu Pro Gln 
                85                  90                  95      


Glu Leu Lys Leu Ile Leu Ser Glu Met Gln Pro Ala Leu Pro Gln Leu 
            100                 105                 110         


Gln Gln His Val Pro Val Leu Lys Asp Ser Ser Leu Leu Phe Glu Glu 
        115                 120                 125             


Phe Lys Lys Leu Ile Arg Asn Arg Gln Ser Glu Ala Ala Asp Ser Ser 
    130                 135                 140                 


Pro Ser Glu Leu Lys Tyr Leu Gly Leu Asp Thr His Ser Arg Lys Lys 
145                 150                 155                 160 


Arg Gln Leu Tyr Ser Ala Leu Ala Asn Lys Cys Cys His Val Gly Cys 
                165                 170                 175     


Thr Lys Arg Ser Leu Ala Arg Phe Cys 
            180                 185 


<210> 4
<211> 185
<212> PRT
<213> Homo sapiens

<400> 4
Met Pro Arg Leu Phe Leu Phe His Leu Leu Glu Phe Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Ala Lys Trp Lys Asp Asp Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


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


Ile Glu Thr Ile Ile Ile Met Leu Glu Phe Ile Ala Asn Leu Pro Pro 
                85                  90                  95      


Glu Leu Lys Ala Ala Leu Ser Glu Arg Gln Pro Ser Leu Pro Glu Leu 
            100                 105                 110         


Gln Gln Tyr Val Pro Ala Leu Lys Asp Ser Asn Leu Ser Phe Glu Glu 
        115                 120                 125             


Phe Lys Lys Leu Ile Arg Asn Arg Gln Ser Glu Ala Ala Asp Ser Asn 
    130                 135                 140                 


Pro Ser Glu Leu Lys Tyr Leu Gly Leu Asp Thr His Ser Gln Lys Lys 
145                 150                 155                 160 


Arg Arg Pro Tyr Val Ala Leu Phe Glu Lys Cys Cys Leu Ile Gly Cys 
                165                 170                 175     


Thr Lys Arg Ser Leu Ala Lys Tyr Cys 
            180                 185 


<210> 5
<211> 185
<212> PRT
<213> Homo sapiens

<400> 5
Met Pro Arg Leu Phe Leu Phe His Leu Leu Glu Phe Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Ala Lys Trp Lys Asp Asp Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


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


Ile Glu Thr Ile Ile Ile Met Leu Glu Phe Ile Ala Asn Leu Pro Pro 
                85                  90                  95      


Glu Leu Lys Ala Ala Leu Ser Glu Arg Gln Pro Ser Leu Pro Glu Leu 
            100                 105                 110         


Gln Gln Tyr Val Pro Ala Leu Lys Asp Ser Asn Leu Ser Phe Glu Glu 
        115                 120                 125             


Phe Lys Lys Leu Ile Arg Asn Arg Gln Ser Glu Ala Ala Asp Ser Asn 
    130                 135                 140                 


Pro Ser Glu Leu Lys Tyr Leu Gly Leu Asp Thr His Ser Gln Lys Lys 
145                 150                 155                 160 


Arg Arg Pro Tyr Val Ala Leu Phe Glu Lys Cys Cys Leu Ile Gly Cys 
                165                 170                 175     


Thr Lys Arg Ser Leu Ala Lys Tyr Cys 
            180                 185 


<210> 6
<211> 92
<212> PRT
<213> Homo sapiens

<400> 6
Met Pro Arg Leu Phe Leu Phe His Leu Leu Glu Phe Cys Leu Leu Leu 
1               5                   10                  15      


Asn Gln Phe Ser Arg Ala Val Ala Ala Lys Trp Lys Asp Asp Val Ile 
            20                  25                  30          


Lys Leu Cys Gly Arg Glu Leu Val Arg Ala Gln Ile Ala Ile Cys Gly 
        35                  40                  45              


Met Ser Thr Trp Ser Lys Arg Ser Leu Ser Gln Glu Asp Ala Pro Gln 
    50                  55                  60                  


Thr Pro Arg Pro Val Ala Gly Ile Ser Ser Ser Leu Leu Arg Arg Arg 
65                  70                  75                  80  


Leu Phe Glu Asp His Asp Gly Pro Ser Phe Leu Val 
                85                  90          


<210> 7
<211> 99
<212> PRT
<213> Homo sapiens

<400> 7
Met Leu Glu Phe Ile Ala Asn Leu Pro Pro Glu Leu Lys Ala Ala Leu 
1               5                   10                  15      


Ser Glu Arg Gln Pro Ser Leu Pro Glu Leu Gln Gln Tyr Val Pro Ala 
            20                  25                  30          


Leu Lys Asp Ser Asn Leu Ser Phe Glu Glu Phe Lys Lys Leu Ile Arg 
        35                  40                  45              


Asn Arg Gln Ser Glu Ala Ala Asp Ser Asn Pro Ser Glu Leu Lys Tyr 
    50                  55                  60                  


Leu Gly Leu Asp Thr His Ser Gln Lys Lys Arg Arg Pro Tyr Val Ala 
65                  70                  75                  80  


Leu Phe Glu Lys Cys Cys Leu Ile Gly Cys Thr Lys Arg Ser Leu Ala 
                85                  90                  95      


Lys Tyr Cys 
            


<210> 8
<211> 142
<212> PRT
<213> Homo sapiens

<400> 8
Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr 
1               5                   10                  15      


Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val 
            20                  25                  30          


Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly 
        35                  40                  45              


Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly 
    50                  55                  60                  


Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu 
65                  70                  75                  80  


Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser 
                85                  90                  95      


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


Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys 
        115                 120                 125             


Cys Lys Trp Gly Cys Ser Lys Ser Glu Ile Ser Ser Leu Cys 
    130                 135                 140         


<210> 9
<211> 142
<212> PRT
<213> Homo sapiens

<400> 9
Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr 
1               5                   10                  15      


Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val 
            20                  25                  30          


Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly 
        35                  40                  45              


Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly 
    50                  55                  60                  


Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu 
65                  70                  75                  80  


Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser 
                85                  90                  95      


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


Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys 
        115                 120                 125             


Cys Lys Trp Gly Cys Ser Lys Ser Glu Ile Ser Ser Leu Cys 
    130                 135                 140         


<210> 10
<211> 142
<212> PRT
<213> Homo sapiens

<400> 10
Met Ala Arg Tyr Met Leu Leu Leu Leu Leu Ala Val Trp Val Leu Thr 
1               5                   10                  15      


Gly Glu Leu Trp Pro Gly Ala Glu Ala Arg Ala Ala Pro Tyr Gly Val 
            20                  25                  30          


Arg Leu Cys Gly Arg Glu Phe Ile Arg Ala Val Ile Phe Thr Cys Gly 
        35                  40                  45              


Gly Ser Arg Trp Arg Arg Ser Asp Ile Leu Ala His Glu Ala Met Gly 
    50                  55                  60                  


Asp Thr Phe Pro Asp Ala Asp Ala Asp Glu Asp Ser Leu Ala Gly Glu 
65                  70                  75                  80  


Leu Asp Glu Ala Met Gly Ser Ser Glu Trp Leu Ala Leu Thr Lys Ser 
                85                  90                  95      


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


Val Leu Arg Gly Ser Arg Asp Val Leu Ala Gly Leu Ser Ser Ser Cys 
        115                 120                 125             


Cys Lys Trp Gly Cys Ser Lys Ser Glu Ile Ser Ser Leu Cys 
    130                 135                 140         


<210> 11
<211> 131
<212> PRT
<213> Homo sapiens

<400> 11
Met Asp Pro Arg Leu Pro Ala Trp Ala Leu Val Leu Leu Gly Pro Ala 
1               5                   10                  15      


Leu Val Phe Ala Leu Gly Pro Ala Pro Thr Pro Glu Met Arg Glu Lys 
            20                  25                  30          


Leu Cys Gly His His Glu Val Arg Ala Leu Val Arg Val Cys Gly Gly 
        35                  40                  45              


Pro Arg Trp Ser Thr Glu Ala Arg Arg Pro Ala Thr Gly Gly Asp Arg 
    50                  55                  60                  


Glu Leu Leu Gln Trp Leu Glu Arg Arg His Leu Leu His Gly Leu Val 
65                  70                  75                  80  


Ala Asp Ser Asn Leu Thr Leu Gly Pro Gly Leu Gln Pro Leu Pro Gln 
                85                  90                  95      


Thr Ser His His His Arg His His Arg Ala Ala Ala Thr Asn Pro Ala 
            100                 105                 110         


Arg Tyr Cys Cys Leu Ser Gly Cys Thr Gln Gln Asp Leu Leu Thr Leu 
        115                 120                 125             


Cys Pro Tyr 
    130     


<210> 12
<211> 139
<212> PRT
<213> Homo sapiens

<400> 12
Met Ala Ser Leu Phe Arg Ser Tyr Leu Pro Ala Ile Trp Leu Leu Leu 
1               5                   10                  15      


Ser Gln Leu Leu Arg Glu Ser Leu Ala Ala Glu Leu Arg Gly Cys Gly 
            20                  25                  30          


Pro Arg Phe Gly Lys His Leu Leu Ser Tyr Cys Pro Met Pro Glu Lys 
        35                  40                  45              


Thr Phe Thr Thr Thr Pro Gly Gly Trp Leu Leu Glu Ser Gly Arg Pro 
    50                  55                  60                  


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


Thr Thr Ser Glu Phe Ile Pro Asn Leu Ser Pro Glu Leu Lys Lys Pro 
                85                  90                  95      


Leu Ser Glu Gly Gln Pro Ser Leu Lys Lys Ile Ile Leu Ser Arg Lys 
            100                 105                 110         


Lys Arg Ser Gly Arg His Arg Phe Asp Pro Phe Cys Cys Glu Val Ile 
        115                 120                 125             


Cys Asp Asp Gly Thr Ser Val Lys Leu Cys Thr 
    130                 135                 


<210> 13
<211> 139
<212> PRT
<213> Homo sapiens

<400> 13
Met Ala Ser Leu Phe Arg Ser Tyr Leu Pro Ala Ile Trp Leu Leu Leu 
1               5                   10                  15      


Ser Gln Leu Leu Arg Glu Ser Leu Ala Ala Glu Leu Arg Gly Cys Gly 
            20                  25                  30          


Pro Arg Phe Gly Lys His Leu Leu Ser Tyr Cys Pro Met Pro Glu Lys 
        35                  40                  45              


Thr Phe Thr Thr Thr Pro Gly Gly Trp Leu Leu Glu Ser Gly Arg Pro 
    50                  55                  60                  


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


Thr Thr Ser Glu Phe Ile Pro Asn Leu Ser Pro Glu Leu Lys Lys Pro 
                85                  90                  95      


Leu Ser Glu Gly Gln Pro Ser Leu Lys Lys Ile Ile Leu Ser Arg Lys 
            100                 105                 110         


Lys Arg Ser Gly Arg His Arg Phe Asp Pro Phe Cys Cys Glu Val Ile 
        115                 120                 125             


Cys Asp Asp Gly Thr Ser Val Lys Leu Cys Thr 
    130                 135                 


<210> 14
<211> 135
<212> PRT
<213> Homo sapiens

<400> 14
Met Lys Gly Ser Ile Phe Thr Leu Phe Leu Phe Ser Val Leu Phe Ala 
1               5                   10                  15      


Ile Ser Glu Val Arg Ser Lys Glu Ser Val Arg Leu Cys Gly Leu Glu 
            20                  25                  30          


Tyr Ile Arg Thr Val Ile Tyr Ile Cys Ala Ser Ser Arg Trp Arg Arg 
        35                  40                  45              


His Leu Glu Gly Ile Pro Gln Ala Gln Gln Ala Glu Thr Gly Asn Ser 
    50                  55                  60                  


Phe Gln Leu Pro His Lys Arg Glu Phe Ser Glu Glu Asn Pro Ala Gln 
65                  70                  75                  80  


Asn Leu Pro Lys Val Asp Ala Ser Gly Glu Asp Arg Leu Trp Gly Gly 
                85                  90                  95      


Gln Met Pro Thr Glu Glu Leu Trp Lys Ser Lys Lys His Ser Val Met 
            100                 105                 110         


Ser Arg Gln Asp Leu Gln Thr Leu Cys Cys Thr Asp Gly Cys Ser Met 
        115                 120                 125             


Thr Asp Leu Ser Ala Leu Cys 
    130                 135 


<210> 15
<211> 135
<212> PRT
<213> Homo sapiens

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


Ile Ser Glu Val Arg Ser Lys Glu Ser Val Arg Leu Cys Gly Leu Glu 
            20                  25                  30          


Tyr Ile Arg Thr Val Ile Tyr Ile Cys Ala Ser Ser Arg Trp Arg Arg 
        35                  40                  45              


His Leu Glu Gly Ile Pro Gln Ala Gln Gln Ala Glu Thr Gly Asn Ser 
    50                  55                  60                  


Phe Gln Leu Pro His Lys Arg Glu Phe Ser Glu Glu Asn Pro Ala Gln 
65                  70                  75                  80  


Asn Leu Pro Lys Val Asp Ala Ser Gly Glu Asp Arg Leu Trp Gly Gly 
                85                  90                  95      


Gln Met Pro Thr Glu Glu Leu Trp Lys Ser Lys Lys His Ser Val Met 
            100                 105                 110         


Ser Arg Gln Asp Leu Gln Thr Leu Cys Cys Thr Asp Gly Cys Ser Met 
        115                 120                 125             


Thr Asp Leu Ser Ala Leu Cys 
    130                 135 


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

<400> 16
Met Pro Arg Leu Leu Arg Leu Ser Leu Leu Trp Leu Gly Leu Leu Leu 
1               5                   10                  15      


Val Arg Phe Ser Arg Glu Leu Ser Asp Ile Ser Ser Ala Arg Lys Leu 
            20                  25                  30          


Cys Gly Arg Tyr Leu Val Lys Glu Ile Glu Lys Leu Cys Gly His Ala 
        35                  40                  45              


Asn Trp Ser Gln Phe Arg Phe Glu Glu Glu Thr Pro Phe Ser Arg Leu 
    50                  55                  60                  


Ile Ala Gln Ala Ser Glu Lys Val Glu Ala Tyr Ser Pro Tyr Gln Phe 
65                  70                  75                  80  


Glu Ser Pro Gln Thr Ala Ser Pro Ala Arg Gly Arg Gly Thr Asn Pro 
                85                  90                  95      


Val Ser Thr Ser Trp Glu Glu Ala Val Asn Ser Trp Glu Met Gln Ser 
            100                 105                 110         


Leu Pro Glu Tyr Lys Asp Lys Lys Gly Tyr Ser Pro Leu Gly Lys Thr 
        115                 120                 125             


Arg Glu Phe Ser Ser Ser His Asn Ile Asn Val Tyr Ile His Glu Asn 
    130                 135                 140                 


Ala Phe Phe Gln Lys Lys Arg Arg Asn Lys Ile Lys Thr Leu Ser Asn 
145                 150                 155                 160 


Leu Phe Trp Gly His His Pro Gln Arg Lys Arg Arg Gly Tyr Ser Glu 
                165                 170                 175     


Lys Cys Cys Leu Thr Gly Cys Thr Lys Glu Glu Leu Ser Ile Ala Cys 
            180                 185                 190         


Leu Pro Tyr Ile Asp Phe Lys Arg Leu Lys Glu Lys Arg Ser Ser Leu 
        195                 200                 205             


Val Thr Lys Ile Tyr 
    210             


