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<110>  The Schepens Eye Research Institute
 
<120>  A New Treatment for Meibomian Gland Dysfunction

<130>  036770-586001WO

<140>  Herewith
<141>  Herewith

<150>  US 62/911,228
<151>  2019-10-05

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  826
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Glu Gly Ala Gly Gly Ala Asn Asp Lys Lys Lys Ile Ser Ser Glu 
1               5                   10                  15      


Arg Arg Lys Glu Lys Ser Arg Asp Ala Ala Arg Ser Arg Arg Ser Lys 
            20                  25                  30          


Glu Ser Glu Val Phe Tyr Glu Leu Ala His Gln Leu Pro Leu Pro His 
        35                  40                  45              


Asn Val Ser Ser His Leu Asp Lys Ala Ser Val Met Arg Leu Thr Ile 
    50                  55                  60                  


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


Glu Asp Asp Met Lys Ala Gln Met Asn Cys Phe Tyr Leu Lys Ala Leu 
                85                  90                  95      


Asp Gly Phe Val Met Val Leu Thr Asp Asp Gly Asp Met Ile Tyr Ile 
            100                 105                 110         


Ser Asp Asn Val Asn Lys Tyr Met Gly Leu Thr Gln Phe Glu Leu Thr 
        115                 120                 125             


Gly His Ser Val Phe Asp Phe Thr His Pro Cys Asp His Glu Glu Met 
    130                 135                 140                 


Arg Glu Met Leu Thr His Arg Asn Gly Leu Val Lys Lys Gly Lys Glu 
145                 150                 155                 160 


Gln Asn Thr Gln Arg Ser Phe Phe Leu Arg Met Lys Cys Thr Leu Thr 
                165                 170                 175     


Ser Arg Gly Arg Thr Met Asn Ile Lys Ser Ala Thr Trp Lys Val Leu 
            180                 185                 190         


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


Gln Cys Gly Tyr Lys Lys Pro Pro Met Thr Cys Leu Val Leu Ile Cys 
    210                 215                 220                 


Glu Pro Ile Pro His Pro Ser Asn Ile Glu Ile Pro Leu Asp Ser Lys 
225                 230                 235                 240 


Thr Phe Leu Ser Arg His Ser Leu Asp Met Lys Phe Ser Tyr Cys Asp 
                245                 250                 255     


Glu Arg Ile Thr Glu Leu Met Gly Tyr Glu Pro Glu Glu Leu Leu Gly 
            260                 265                 270         


Arg Ser Ile Tyr Glu Tyr Tyr His Ala Leu Asp Ser Asp His Leu Thr 
        275                 280                 285             


Lys Thr His His Asp Met Phe Thr Lys Gly Gln Val Thr Thr Gly Gln 
    290                 295                 300                 


Tyr Arg Met Leu Ala Lys Arg Gly Gly Tyr Val Trp Val Glu Thr Gln 
305                 310                 315                 320 


Ala Thr Val Ile Tyr Asn Thr Lys Asn Ser Gln Pro Gln Cys Ile Val 
                325                 330                 335     


Cys Val Asn Tyr Val Val Ser Gly Ile Ile Gln His Asp Leu Ile Phe 
            340                 345                 350         


Ser Leu Gln Gln Thr Glu Cys Val Leu Lys Pro Val Glu Ser Ser Asp 
        355                 360                 365             


Met Lys Met Thr Gln Leu Phe Thr Lys Val Glu Ser Glu Asp Thr Ser 
    370                 375                 380                 


Ser Leu Phe Asp Lys Leu Lys Lys Glu Pro Asp Ala Leu Thr Leu Leu 
385                 390                 395                 400 


Ala Pro Ala Ala Gly Asp Thr Ile Ile Ser Leu Asp Phe Gly Ser Asn 
                405                 410                 415     


Asp Thr Glu Thr Asp Asp Gln Gln Leu Glu Glu Val Pro Leu Tyr Asn 
            420                 425                 430         


Asp Val Met Leu Pro Ser Pro Asn Glu Lys Leu Gln Asn Ile Asn Leu 
        435                 440                 445             


Ala Met Ser Pro Leu Pro Thr Ala Glu Thr Pro Lys Pro Leu Arg Ser 
    450                 455                 460                 


Ser Ala Asp Pro Ala Leu Asn Gln Glu Val Ala Leu Lys Leu Glu Pro 
465                 470                 475                 480 


Asn Pro Glu Ser Leu Glu Leu Ser Phe Thr Met Pro Gln Ile Gln Asp 
                485                 490                 495     


Gln Thr Pro Ser Pro Ser Asp Gly Ser Thr Arg Gln Ser Ser Pro Glu 
            500                 505                 510         


Pro Asn Ser Pro Ser Glu Tyr Cys Phe Tyr Val Asp Ser Asp Met Val 
        515                 520                 525             


Asn Glu Phe Lys Leu Glu Leu Val Glu Lys Leu Phe Ala Glu Asp Thr 
    530                 535                 540                 


Glu Ala Lys Asn Pro Phe Ser Thr Gln Asp Thr Asp Leu Asp Leu Glu 
545                 550                 555                 560 


Met Leu Ala Pro Tyr Ile Pro Met Asp Asp Asp Phe Gln Leu Arg Ser 
                565                 570                 575     


Phe Asp Gln Leu Ser Pro Leu Glu Ser Ser Ser Ala Ser Pro Glu Ser 
            580                 585                 590         


Ala Ser Pro Gln Ser Thr Val Thr Val Phe Gln Gln Thr Gln Ile Gln 
        595                 600                 605             


Glu Pro Thr Ala Asn Ala Thr Thr Thr Thr Ala Thr Thr Asp Glu Leu 
    610                 615                 620                 


Lys Thr Val Thr Lys Asp Arg Met Glu Asp Ile Lys Ile Leu Ile Ala 
625                 630                 635                 640 


Ser Pro Ser Pro Thr His Ile His Lys Glu Thr Thr Ser Ala Thr Ser 
                645                 650                 655     


Ser Pro Tyr Arg Asp Thr Gln Ser Arg Thr Ala Ser Pro Asn Arg Ala 
            660                 665                 670         


Gly Lys Gly Val Ile Glu Gln Thr Glu Lys Ser His Pro Arg Ser Pro 
        675                 680                 685             


Asn Val Leu Ser Val Ala Leu Ser Gln Arg Thr Thr Val Pro Glu Glu 
    690                 695                 700                 


Glu Leu Asn Pro Lys Ile Leu Ala Leu Gln Asn Ala Gln Arg Lys Arg 
705                 710                 715                 720 


Lys Met Glu His Asp Gly Ser Leu Phe Gln Ala Val Gly Ile Gly Thr 
                725                 730                 735     


Leu Leu Gln Gln Pro Asp Asp His Ala Ala Thr Thr Ser Leu Ser Trp 
            740                 745                 750         


Lys Arg Val Lys Gly Cys Lys Ser Ser Glu Gln Asn Gly Met Glu Gln 
        755                 760                 765             


Lys Thr Ile Ile Leu Ile Pro Ser Asp Leu Ala Cys Arg Leu Leu Gly 
    770                 775                 780                 


Gln Ser Met Asp Glu Ser Gly Leu Pro Gln Leu Thr Ser Tyr Asp Cys 
785                 790                 795                 800 


Glu Val Asn Ala Pro Ile Gln Gly Ser Arg Asn Leu Leu Gln Gly Glu 
                805                 810                 815     


Glu Leu Leu Arg Ala Leu Asp Gln Val Asn 
            820                 825     


<210>  2
<211>  870
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Thr Ala Asp Lys Glu Lys Lys Arg Ser Ser Ser Glu Arg Arg Lys 
1               5                   10                  15      


Glu Lys Ser Arg Asp Ala Ala Arg Cys Arg Arg Ser Lys Glu Thr Glu 
            20                  25                  30          


Val Phe Tyr Glu Leu Ala His Glu Leu Pro Leu Pro His Ser Val Ser 
        35                  40                  45              


Ser His Leu Asp Lys Ala Ser Ile Met Arg Leu Ala Ile Ser Phe Leu 
    50                  55                  60                  


Arg Thr His Lys Leu Leu Ser Ser Val Cys Ser Glu Asn Glu Ser Glu 
65                  70                  75                  80  


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


Gly Phe Ile Ala Val Val Thr Gln Asp Gly Asp Met Ile Phe Leu Ser 
            100                 105                 110         


Glu Asn Ile Ser Lys Phe Met Gly Leu Thr Gln Val Glu Leu Thr Gly 
        115                 120                 125             


His Ser Ile Phe Asp Phe Thr His Pro Cys Asp His Glu Glu Ile Arg 
    130                 135                 140                 


Glu Asn Leu Ser Leu Lys Asn Gly Ser Gly Phe Gly Lys Lys Ser Lys 
145                 150                 155                 160 


Asp Met Ser Thr Glu Arg Asp Phe Phe Met Arg Met Lys Cys Thr Val 
                165                 170                 175     


Thr Asn Arg Gly Arg Thr Val Asn Leu Lys Ser Ala Thr Trp Lys Val 
            180                 185                 190         


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


Asn Ser Leu Cys Gly Tyr Lys Glu Pro Leu Leu Ser Cys Leu Ile Ile 
    210                 215                 220                 


Met Cys Glu Pro Ile Gln His Pro Ser His Met Asp Ile Pro Leu Asp 
225                 230                 235                 240 


Ser Lys Thr Phe Leu Ser Arg His Ser Met Asp Met Lys Phe Thr Tyr 
                245                 250                 255     


Cys Asp Asp Arg Ile Thr Glu Leu Ile Gly Tyr His Pro Glu Glu Leu 
            260                 265                 270         


Leu Gly Arg Ser Ala Tyr Glu Phe Tyr His Ala Leu Asp Ser Glu Asn 
        275                 280                 285             


Met Thr Lys Ser His Gln Asn Leu Cys Thr Lys Gly Gln Val Val Ser 
    290                 295                 300                 


Gly Gln Tyr Arg Met Leu Ala Lys His Gly Gly Tyr Val Trp Leu Glu 
305                 310                 315                 320 


Thr Gln Gly Thr Val Ile Tyr Asn Pro Arg Asn Leu Gln Pro Gln Cys 
                325                 330                 335     


Ile Met Cys Val Asn Tyr Val Leu Ser Glu Ile Glu Lys Asn Asp Val 
            340                 345                 350         


Val Phe Ser Met Asp Gln Thr Glu Ser Leu Phe Lys Pro His Leu Met 
        355                 360                 365             


Ala Met Asn Ser Ile Phe Asp Ser Ser Gly Lys Gly Ala Val Ser Glu 
    370                 375                 380                 


Lys Ser Asn Phe Leu Phe Thr Lys Leu Lys Glu Glu Pro Glu Glu Leu 
385                 390                 395                 400 


Ala Gln Leu Ala Pro Thr Pro Gly Asp Ala Ile Ile Ser Leu Asp Phe 
                405                 410                 415     


Gly Asn Gln Asn Phe Glu Glu Ser Ser Ala Tyr Gly Lys Ala Ile Leu 
            420                 425                 430         


Pro Pro Ser Gln Pro Trp Ala Thr Glu Leu Arg Ser His Ser Thr Gln 
        435                 440                 445             


Ser Glu Ala Gly Ser Leu Pro Ala Phe Thr Val Pro Gln Ala Ala Ala 
    450                 455                 460                 


Pro Gly Ser Thr Thr Pro Ser Ala Thr Ser Ser Ser Ser Ser Cys Ser 
465                 470                 475                 480 


Thr Pro Asn Ser Pro Glu Asp Tyr Tyr Thr Ser Leu Asp Asn Asp Leu 
                485                 490                 495     


Lys Ile Glu Val Ile Glu Lys Leu Phe Ala Met Asp Thr Glu Ala Lys 
            500                 505                 510         


Asp Gln Cys Ser Thr Gln Thr Asp Phe Asn Glu Leu Asp Leu Glu Thr 
        515                 520                 525             


Leu Ala Pro Tyr Ile Pro Met Asp Gly Glu Asp Phe Gln Leu Ser Pro 
    530                 535                 540                 


Ile Cys Pro Glu Glu Arg Leu Leu Ala Glu Asn Pro Gln Ser Thr Pro 
545                 550                 555                 560 


Gln His Cys Phe Ser Ala Met Thr Asn Ile Phe Gln Pro Leu Ala Pro 
                565                 570                 575     


Val Ala Pro His Ser Pro Phe Leu Leu Asp Lys Phe Gln Gln Gln Leu 
            580                 585                 590         


Glu Ser Lys Lys Thr Glu Pro Glu His Arg Pro Met Ser Ser Ile Phe 
        595                 600                 605             


Phe Asp Ala Gly Ser Lys Ala Ser Leu Pro Pro Cys Cys Gly Gln Ala 
    610                 615                 620                 


Ser Thr Pro Leu Ser Ser Met Gly Gly Arg Ser Asn Thr Gln Trp Pro 
625                 630                 635                 640 


Pro Asp Pro Pro Leu His Phe Gly Pro Thr Lys Trp Ala Val Gly Asp 
                645                 650                 655     


Gln Arg Thr Glu Phe Leu Gly Ala Ala Pro Leu Gly Pro Pro Val Ser 
            660                 665                 670         


Pro Pro His Val Ser Thr Phe Lys Thr Arg Ser Ala Lys Gly Phe Gly 
        675                 680                 685             


Ala Arg Gly Pro Asp Val Leu Ser Pro Ala Met Val Ala Leu Ser Asn 
    690                 695                 700                 


Lys Leu Lys Leu Lys Arg Gln Leu Glu Tyr Glu Glu Gln Ala Phe Gln 
705                 710                 715                 720 


Asp Leu Ser Gly Gly Asp Pro Pro Gly Gly Ser Thr Ser His Leu Met 
                725                 730                 735     


Trp Lys Arg Met Lys Asn Leu Arg Gly Gly Ser Cys Pro Leu Met Pro 
            740                 745                 750         


Asp Lys Pro Leu Ser Ala Asn Val Pro Asn Asp Lys Phe Thr Gln Asn 
        755                 760                 765             


Pro Met Arg Gly Leu Gly His Pro Leu Arg His Leu Pro Leu Pro Gln 
    770                 775                 780                 


Pro Pro Ser Ala Ile Ser Pro Gly Glu Asn Ser Lys Ser Arg Phe Pro 
785                 790                 795                 800 


Pro Gln Cys Tyr Ala Thr Gln Tyr Gln Asp Tyr Ser Leu Ser Ser Ala 
                805                 810                 815     


His Lys Val Ser Gly Met Ala Ser Arg Leu Leu Gly Pro Ser Phe Glu 
            820                 825                 830         


Ser Tyr Leu Leu Pro Glu Leu Thr Arg Tyr Asp Cys Glu Val Asn Val 
        835                 840                 845             


Pro Val Leu Gly Ser Ser Thr Leu Leu Gln Gly Gly Asp Leu Leu Arg 
    850                 855                 860                 


Ala Leu Asp Gln Ala Thr 
865                 870 


<210>  3
<211>  669
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Ala Leu Gly Leu Gln Arg Ala Arg Ser Thr Thr Glu Leu Arg Lys 
1               5                   10                  15      


Glu Lys Ser Arg Asp Ala Ala Arg Ser Arg Arg Ser Gln Glu Thr Glu 
            20                  25                  30          


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


Ala His Leu Asp Lys Ala Ser Ile Met Arg Leu Thr Ile Ser Tyr Leu 
    50                  55                  60                  


Arg Met His Arg Leu Cys Ala Ala Gly Glu Trp Asn Gln Val Gly Ala 
65                  70                  75                  80  


Gly Gly Glu Pro Leu Asp Ala Cys Tyr Leu Lys Ala Leu Glu Gly Phe 
                85                  90                  95      


Val Met Val Leu Thr Ala Glu Gly Asp Met Ala Tyr Leu Ser Glu Asn 
            100                 105                 110         


Val Ser Lys His Leu Gly Leu Ser Gln Leu Glu Leu Ile Gly His Ser 
        115                 120                 125             


Ile Phe Asp Phe Ile His Pro Cys Asp Gln Glu Glu Leu Gln Asp Ala 
    130                 135                 140                 


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


Glu Arg Cys Phe Ser Leu Arg Met Lys Ser Thr Leu Thr Ser Arg Gly 
                165                 170                 175     


Arg Thr Leu Asn Leu Lys Ala Ala Thr Trp Lys Val Leu Asn Cys Ser 
            180                 185                 190         


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


Ser Pro Asp Ser Glu Pro Pro Leu Gln Cys Leu Val Leu Ile Cys Glu 
    210                 215                 220                 


Ala Ile Pro His Pro Gly Ser Leu Glu Pro Pro Leu Gly Arg Gly Ala 
225                 230                 235                 240 


Phe Leu Ser Arg His Ser Leu Asp Met Lys Phe Thr Tyr Cys Asp Asp 
                245                 250                 255     


Arg Ile Ala Glu Val Ala Gly Tyr Ser Pro Asp Asp Leu Ile Gly Cys 
            260                 265                 270         


Ser Ala Tyr Glu Tyr Ile His Ala Leu Asp Ser Asp Ala Val Ser Lys 
        275                 280                 285             


Ser Ile His Thr Leu Leu Ser Lys Gly Gln Ala Val Thr Gly Gln Tyr 
    290                 295                 300                 


Arg Phe Leu Ala Arg Ser Gly Gly Tyr Leu Trp Thr Gln Thr Gln Ala 
305                 310                 315                 320 


Thr Val Val Ser Gly Gly Arg Gly Pro Gln Ser Glu Ser Ile Val Cys 
                325                 330                 335     


Val His Phe Leu Ile Ser Gln Val Glu Glu Thr Gly Val Val Leu Ser 
            340                 345                 350         


Leu Glu Gln Thr Glu Gln His Ser Arg Arg Pro Ile Gln Arg Gly Ala 
        355                 360                 365             


Pro Ser Gln Lys Asp Thr Pro Asn Pro Gly Asp Ser Leu Asp Thr Pro 
    370                 375                 380                 


Gly Pro Arg Ile Leu Ala Phe Leu His Pro Pro Ser Leu Ser Glu Ala 
385                 390                 395                 400 


Ala Leu Ala Ala Asp Pro Arg Arg Phe Cys Ser Pro Asp Leu Arg Arg 
                405                 410                 415     


Leu Leu Gly Pro Ile Leu Asp Gly Ala Ser Val Ala Ala Thr Pro Ser 
            420                 425                 430         


Thr Pro Leu Ala Thr Arg His Pro Gln Ser Pro Leu Ser Ala Asp Leu 
        435                 440                 445             


Pro Asp Glu Leu Pro Val Gly Thr Glu Asn Val His Arg Leu Phe Thr 
    450                 455                 460                 


Ser Gly Lys Asp Thr Glu Ala Val Glu Thr Asp Leu Asp Ile Ala Gln 
465                 470                 475                 480 


Asp Ala Asp Ala Leu Asp Leu Glu Met Leu Ala Pro Tyr Ile Ser Met 
                485                 490                 495     


Asp Asp Asp Phe Gln Leu Asn Ala Ser Glu Gln Leu Pro Arg Ala Tyr 
            500                 505                 510         


His Arg Pro Leu Gly Ala Val Pro Arg Pro Arg Ala Arg Ser Phe His 
        515                 520                 525             


Gly Leu Ser Pro Pro Ala Leu Glu Pro Ser Leu Leu Pro Arg Trp Gly 
    530                 535                 540                 


Ser Asp Pro Arg Leu Ser Cys Ser Ser Pro Ser Arg Gly Asp Pro Ser 
545                 550                 555                 560 


Ala Ser Ser Pro Met Ala Gly Ala Arg Lys Arg Thr Leu Ala Gln Ser 
                565                 570                 575     


Ser Glu Asp Glu Asp Glu Gly Val Glu Leu Leu Gly Val Arg Pro Pro 
            580                 585                 590         


Lys Arg Ser Pro Ser Pro Glu His Glu Asn Phe Leu Leu Phe Pro Leu 
        595                 600                 605             


Ser Leu Ser Phe Leu Leu Thr Gly Gly Pro Ala Pro Gly Ser Leu Gln 
    610                 615                 620                 


Asp Pro Ser Thr Pro Leu Leu Asn Leu Asn Glu Pro Leu Gly Leu Gly 
625                 630                 635                 640 


Pro Ser Leu Leu Ser Pro Tyr Ser Asp Glu Asp Thr Thr Gln Pro Gly 
                645                 650                 655     


Gly Pro Phe Gln Pro Arg Ala Gly Ser Ala Gln Ala Asp 
            660                 665                 


