                         SEQUENCE LISTING

<110>  Instituto de Medicina Molecular Joo Lobo Antunes
       Universidade de Coimbra
       Faculdade de Medicina da Universidade de Lisboa
 
<120>  Therapeutic Agents, Pharmaceutical Compositions, and Associated 
       Biomarkers

<130>  IMMJ-001/01WO

<150>  GB2004832.8
<151>  2020-04-01

<160>  28    

<170>  PatentIn version 3.5

<210>  1
<211>  821
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ser Pro Trp Leu Lys Trp His Gly Pro Ala Met Ala Arg Leu Trp 
1               5                   10                  15      


Gly Leu Cys Leu Leu Val Leu Gly Phe Trp Arg Ala Ser Leu Ala Cys 
            20                  25                  30          


Pro Thr Ser Cys Lys Cys Ser Ser Ala Arg Ile Trp Cys Thr Glu Pro 
        35                  40                  45              


Ser Pro Gly Ile Val Ala Phe Pro Arg Leu Glu Pro Asn Ser Val Asp 
    50                  55                  60                  


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


Ile Ile Asn Glu Asp Asp Val Glu Ala Tyr Val Gly Leu Arg Asn Leu 
                85                  90                  95      


Thr Ile Val Asp Ser Gly Leu Lys Phe Val Ala Tyr Lys Ala Phe Leu 
            100                 105                 110         


Lys Asn Ser Asn Leu Arg His Ile Asn Phe Thr Arg Asn Lys Leu Thr 
        115                 120                 125             


Ser Leu Ser Arg Arg His Phe Arg His Leu Asp Leu Ser Asp Leu Ile 
    130                 135                 140                 


Leu Thr Gly Asn Pro Phe Thr Cys Ser Cys Asp Ile Met Trp Leu Lys 
145                 150                 155                 160 


Thr Leu Gln Glu Thr Lys Ser Ser Pro Asp Thr Gln Asp Leu Tyr Cys 
                165                 170                 175     


Leu Asn Glu Ser Ser Lys Asn Met Pro Leu Ala Asn Leu Gln Ile Pro 
            180                 185                 190         


Asn Cys Gly Leu Pro Ser Ala Arg Leu Ala Ala Pro Asn Leu Thr Val 
        195                 200                 205             


Glu Glu Gly Lys Ser Val Thr Leu Ser Cys Ser Val Gly Gly Asp Pro 
    210                 215                 220                 


Leu Pro Thr Leu Tyr Trp Asp Val Gly Asn Leu Val Ser Lys His Met 
225                 230                 235                 240 


Asn Glu Thr Ser His Thr Gln Gly Ser Leu Arg Ile Thr Asn Ile Ser 
                245                 250                 255     


Ser Asp Asp Ser Gly Lys Gln Ile Ser Cys Val Ala Glu Asn Leu Val 
            260                 265                 270         


Gly Glu Asp Gln Asp Ser Val Asn Leu Thr Val His Phe Ala Pro Thr 
        275                 280                 285             


Ile Thr Phe Leu Glu Ser Pro Thr Ser Asp His His Trp Cys Ile Pro 
    290                 295                 300                 


Phe Thr Val Arg Gly Asn Pro Lys Pro Ala Leu Gln Trp Phe Tyr Asn 
305                 310                 315                 320 


Gly Ala Ile Leu Asn Glu Ser Lys Tyr Ile Cys Thr Lys Ile His Val 
                325                 330                 335     


Thr Asn His Thr Glu Tyr His Gly Cys Leu Gln Leu Asp Asn Pro Thr 
            340                 345                 350         


His Met Asn Asn Gly Asp Tyr Thr Leu Met Ala Lys Asn Glu Tyr Gly 
        355                 360                 365             


Lys Asp Glu Arg Gln Ile Ser Ala His Phe Met Gly Arg Pro Gly Val 
    370                 375                 380                 


Asp Tyr Glu Thr Asn Pro Asn Tyr Pro Glu Val Leu Tyr Glu Asp Trp 
385                 390                 395                 400 


Thr Thr Pro Thr Asp Ile Gly Asp Thr Thr Asn Lys Ser Asn Glu Ile 
                405                 410                 415     


Pro Ser Thr Asp Val Ala Asp Gln Ser Asn Arg Glu His Leu Ser Val 
            420                 425                 430         


Tyr Ala Val Val Val Ile Ala Ser Val Val Gly Phe Cys Leu Leu Val 
        435                 440                 445             


Met Leu Leu Leu Leu Lys Leu Ala Arg His Ser Lys Phe Gly Met Lys 
    450                 455                 460                 


Gly Pro Ala Ser Val Ile Ser Asn Asp Asp Asp Ser Ala Ser Pro Leu 
465                 470                 475                 480 


His His Ile Ser Asn Gly Ser Asn Thr Pro Ser Ser Ser Glu Gly Gly 
                485                 490                 495     


Pro Asp Ala Val Ile Ile Gly Met Thr Lys Ile Pro Val Ile Glu Asn 
            500                 505                 510         


Pro Gln Tyr Phe Gly Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr Phe 
        515                 520                 525             


Val Gln His Ile Lys Arg His Asn Ile Val Leu Lys Arg Glu Leu Gly 
    530                 535                 540                 


Glu Gly Ala Phe Gly Lys Val Phe Leu Ala Glu Cys Tyr Asn Leu Cys 
545                 550                 555                 560 


Pro Glu Gln Asp Lys Ile Leu Val Ala Val Lys Thr Leu Lys Asp Ala 
                565                 570                 575     


Ser Asp Asn Ala Arg Lys Asp Phe His Arg Glu Ala Glu Leu Leu Thr 
            580                 585                 590         


Asn Leu Gln His Glu His Ile Val Lys Phe Tyr Gly Val Cys Val Glu 
        595                 600                 605             


Gly Asp Pro Leu Ile Met Val Phe Glu Tyr Met Lys His Gly Asp Leu 
    610                 615                 620                 


Asn Lys Phe Leu Arg Ala His Gly Pro Asp Ala Val Leu Met Ala Glu 
625                 630                 635                 640 


Gly Asn Pro Pro Thr Glu Leu Thr Gln Ser Gln Met Leu His Ile Ala 
                645                 650                 655     


Gln Gln Ile Ala Ala Gly Met Val Tyr Leu Ala Ser Gln His Phe Val 
            660                 665                 670         


His Arg Asp Leu Ala Thr Arg Asn Cys Leu Val Gly Glu Asn Leu Leu 
        675                 680                 685             


Val Lys Ile Gly Asp Phe Gly Met Ser Arg Asp Val Tyr Ser Thr Asp 
    690                 695                 700                 


Tyr Tyr Arg Val Gly Gly His Thr Met Leu Pro Ile Arg Trp Met Pro 
705                 710                 715                 720 


Pro Glu Ser Ile Met Tyr Arg Lys Phe Thr Thr Glu Ser Asp Val Trp 
                725                 730                 735     


Ser Leu Gly Val Val Leu Trp Glu Ile Phe Thr Tyr Gly Lys Gln Pro 
            740                 745                 750         


Trp Tyr Gln Leu Ser Asn Asn Glu Val Ile Glu Cys Ile Thr Gln Gly 
        755                 760                 765             


Arg Val Leu Gln Arg Pro Arg Thr Cys Pro Gln Glu Val Tyr Glu Leu 
    770                 775                 780                 


Met Leu Gly Cys Trp Gln Arg Glu Pro His Thr Arg Lys Asn Ile Lys 
785                 790                 795                 800 


Ser Ile His Thr Leu Leu Gln Asn Leu Ala Lys Ala Ser Pro Val Tyr 
                805                 810                 815     


Leu Asp Ile Leu Gly 
            820     


<210>  2
<211>  301
<212>  PRT
<213>  Homo sapiens

<400>  2

Ser Gln Leu Lys Pro Asp Thr Phe Val Gln His Ile Lys Arg His Asn 
1               5                   10                  15      


Ile Val Leu Lys Arg Glu Leu Gly Glu Gly Ala Phe Gly Lys Val Phe 
            20                  25                  30          


Leu Ala Glu Cys Tyr Asn Leu Cys Pro Glu Gln Asp Lys Ile Leu Val 
        35                  40                  45              


Ala Val Lys Thr Leu Lys Asp Ala Ser Asp Asn Ala Arg Lys Asp Phe 
    50                  55                  60                  


His Arg Glu Ala Glu Leu Leu Thr Asn Leu Gln His Glu His Ile Val 
65                  70                  75                  80  


Lys Phe Tyr Gly Val Cys Val Glu Gly Asp Pro Leu Ile Met Val Phe 
                85                  90                  95      


Glu Tyr Met Lys His Gly Asp Leu Asn Lys Phe Leu Arg Ala His Gly 
            100                 105                 110         


Pro Asp Ala Val Leu Met Ala Glu Gly Asn Pro Pro Thr Glu Leu Thr 
        115                 120                 125             


Gln Ser Gln Met Leu His Ile Ala Gln Gln Ile Ala Ala Gly Met Val 
    130                 135                 140                 


Tyr Leu Ala Ser Gln His Phe Val His Arg Asp Leu Ala Thr Arg Asn 
145                 150                 155                 160 


Cys Leu Val Gly Glu Asn Leu Leu Val Lys Ile Gly Asp Phe Gly Met 
                165                 170                 175     


Ser Arg Asp Val Tyr Ser Thr Asp Tyr Tyr Arg Val Gly Gly His Thr 
            180                 185                 190         


Met Leu Pro Ile Arg Trp Met Pro Pro Glu Ser Ile Met Tyr Arg Lys 
        195                 200                 205             


Phe Thr Thr Glu Ser Asp Val Trp Ser Leu Gly Val Val Leu Trp Glu 
    210                 215                 220                 


Ile Phe Thr Tyr Gly Lys Gln Pro Trp Tyr Gln Leu Ser Asn Asn Glu 
225                 230                 235                 240 


Val Ile Glu Cys Ile Thr Gln Gly Arg Val Leu Gln Arg Pro Arg Thr 
                245                 250                 255     


Cys Pro Gln Glu Val Tyr Glu Leu Met Leu Gly Cys Trp Gln Arg Glu 
            260                 265                 270         


Pro His Thr Arg Lys Asn Ile Lys Ser Ile His Thr Leu Leu Gln Asn 
        275                 280                 285             


Leu Ala Lys Ala Ser Pro Val Tyr Leu Asp Ile Leu Gly 
    290                 295                 300     


<210>  3
<211>  520
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Ser Pro Trp Leu Lys Trp His Gly Pro Ala Met Ala Arg Leu Trp 
1               5                   10                  15      


Gly Leu Cys Leu Leu Val Leu Gly Phe Trp Arg Ala Ser Leu Ala Cys 
            20                  25                  30          


Pro Thr Ser Cys Lys Cys Ser Ser Ala Arg Ile Trp Cys Thr Glu Pro 
        35                  40                  45              


Ser Pro Gly Ile Val Ala Phe Pro Arg Leu Glu Pro Asn Ser Val Asp 
    50                  55                  60                  


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


Ile Ile Asn Glu Asp Asp Val Glu Ala Tyr Val Gly Leu Arg Asn Leu 
                85                  90                  95      


Thr Ile Val Asp Ser Gly Leu Lys Phe Val Ala Tyr Lys Ala Phe Leu 
            100                 105                 110         


Lys Asn Ser Asn Leu Arg His Ile Asn Phe Thr Arg Asn Lys Leu Thr 
        115                 120                 125             


Ser Leu Ser Arg Arg His Phe Arg His Leu Asp Leu Ser Asp Leu Ile 
    130                 135                 140                 


Leu Thr Gly Asn Pro Phe Thr Cys Ser Cys Asp Ile Met Trp Leu Lys 
145                 150                 155                 160 


Thr Leu Gln Glu Thr Lys Ser Ser Pro Asp Thr Gln Asp Leu Tyr Cys 
                165                 170                 175     


Leu Asn Glu Ser Ser Lys Asn Met Pro Leu Ala Asn Leu Gln Ile Pro 
            180                 185                 190         


Asn Cys Gly Leu Pro Ser Ala Arg Leu Ala Ala Pro Asn Leu Thr Val 
        195                 200                 205             


Glu Glu Gly Lys Ser Val Thr Leu Ser Cys Ser Val Gly Gly Asp Pro 
    210                 215                 220                 


Leu Pro Thr Leu Tyr Trp Asp Val Gly Asn Leu Val Ser Lys His Met 
225                 230                 235                 240 


Asn Glu Thr Ser His Thr Gln Gly Ser Leu Arg Ile Thr Asn Ile Ser 
                245                 250                 255     


Ser Asp Asp Ser Gly Lys Gln Ile Ser Cys Val Ala Glu Asn Leu Val 
            260                 265                 270         


Gly Glu Asp Gln Asp Ser Val Asn Leu Thr Val His Phe Ala Pro Thr 
        275                 280                 285             


Ile Thr Phe Leu Glu Ser Pro Thr Ser Asp His His Trp Cys Ile Pro 
    290                 295                 300                 


Phe Thr Val Arg Gly Asn Pro Lys Pro Ala Leu Gln Trp Phe Tyr Asn 
305                 310                 315                 320 


Gly Ala Ile Leu Asn Glu Ser Lys Tyr Ile Cys Thr Lys Ile His Val 
                325                 330                 335     


Thr Asn His Thr Glu Tyr His Gly Cys Leu Gln Leu Asp Asn Pro Thr 
            340                 345                 350         


His Met Asn Asn Gly Asp Tyr Thr Leu Met Ala Lys Asn Glu Tyr Gly 
        355                 360                 365             


Lys Asp Glu Arg Gln Ile Ser Ala His Phe Met Gly Arg Pro Gly Val 
    370                 375                 380                 


Asp Tyr Glu Thr Asn Pro Asn Tyr Pro Glu Val Leu Tyr Glu Asp Trp 
385                 390                 395                 400 


Thr Thr Pro Thr Asp Ile Gly Asp Thr Thr Asn Lys Ser Asn Glu Ile 
                405                 410                 415     


Pro Ser Thr Asp Val Ala Asp Gln Ser Asn Arg Glu His Leu Ser Val 
            420                 425                 430         


Tyr Ala Val Val Val Ile Ala Ser Val Val Gly Phe Cys Leu Leu Val 
        435                 440                 445             


Met Leu Leu Leu Leu Lys Leu Ala Arg His Ser Lys Phe Gly Met Lys 
    450                 455                 460                 


Gly Pro Ala Ser Val Ile Ser Asn Asp Asp Asp Ser Ala Ser Pro Leu 
465                 470                 475                 480 


His His Ile Ser Asn Gly Ser Asn Thr Pro Ser Ser Ser Glu Gly Gly 
                485                 490                 495     


Pro Asp Ala Val Ile Ile Gly Met Thr Lys Ile Pro Val Ile Glu Asn 
            500                 505                 510         


Pro Gln Tyr Phe Gly Ile Thr Asn 
        515                 520 


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

<220>
<223>  Artificial peptide

<400>  4

Gly Ile Thr Asn 
1               


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

<220>
<223>  Artificial peptide

<400>  5

Phe Gly Ile Thr Asn 
1               5   


<210>  6
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  6

Tyr Phe Gly Ile Thr Asn 
1               5       


<210>  7
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  7

Gln Tyr Phe Gly Ile Thr Asn 
1               5           


<210>  8
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  8

Pro Gln Tyr Phe Gly Ile Thr Asn 
1               5               


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

<220>
<223>  Artificial peptide

<400>  9

Asn Pro Gln Tyr Phe Gly Ile Thr Asn 
1               5                   


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

<220>
<223>  Artificial peptide

<400>  10

Glu Asn Pro Gln Tyr Phe Gly Ile Thr Asn 
1               5                   10  


<210>  11
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  11

Ser Gln Leu Lys 
1               


<210>  12
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  12

Ser Gln Leu Lys Pro 
1               5   


<210>  13
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  13

Ser Gln Leu Lys Pro Asp 
1               5       


<210>  14
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  14

Ser Gln Leu Lys Pro Asp Thr 
1               5           


<210>  15
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  15

Ser Gln Leu Lys Pro Asp Thr Phe 
1               5               


<210>  16
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  16

Ser Gln Leu Lys Pro Asp Thr Phe Val 
1               5                   


<210>  17
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  17

Ser Gln Leu Lys Pro Asp Thr Phe Val Gln 
1               5                   10  


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

<220>
<223>  Artificial peptide

<400>  18

Phe Gly Ile Thr Asn Ser Gln Leu Lys Pro 
1               5                   10  


<210>  19
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  19

Pro Gln Tyr Phe Gly Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr Phe 
1               5                   10                  15      


<210>  20
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  20

Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr Phe Val Gln His 
1               5                   10                  


<210>  21
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  21

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


<210>  22
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  22

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Lys Lys Phe Gly Ile 
1               5                   10                  15      


Thr Asn Ser Gln Leu Lys Pro 
            20              


<210>  23
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  23

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Lys Lys Pro Gln Tyr 
1               5                   10                  15      


Phe Gly Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr Phe 
            20                  25                  


<210>  24
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  24

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Lys Lys Ile Thr Asn 
1               5                   10                  15      


Ser Gln Leu Lys Pro Asp Thr Phe Val Gln His 
            20                  25          


<210>  25
<211>  27
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  25

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Gln Tyr Phe Gly 
1               5                   10                  15      


Ile Thr Asn Ser Gln Leu Lys Pro Asp Thr Phe 
            20                  25          


<210>  26
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  26

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Phe Gly Ile 
1               5                   10                  15      


Thr Asn Ser Gln Leu Lys Pro 
            20              


<210>  27
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  27

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gln Phe Gly Ile Thr 
1               5                   10                  15      


Asn Ser Gln Leu Lys Pro 
            20          


<210>  28
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Artificial peptide

<400>  28

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Glu Phe Gly Ile Thr 
1               5                   10                  15      


Asn Ser Gln Leu Lys Pro 
            20          


