                         SEQUENCE LISTING

<110>  MERCK PATENT GMBH 
 
<120>  Markers useful in enrichment strategies for the treatment of 
       osteoarthritis

<130>  P 18/139 

<150>  EP18193351.6
<151>  10.09.2018

<160>  10    

<170>  PatentIn version 3.5


<210>  1
<211>  6
<212>  PRT
<213>  recombinant

<220>
<223>  Marker CTX-II

<400>  1

Glu Lys Gly Pro Asp Pro
1               5      


<210>  2
<211>  10
<212>  PRT
<213>  recombinant

<220>
<223>  Marker ProC2

<400>  2

Gln Asp Val Arg Gln Pro Gly Pro Lys Gly
1               5                   10    


<210>  3
<211>  207
<212>  PRT
<213>  Homo sapiens

<220>
<223>  Native human FGF-18

<400>  3

Met Tyr Ser Ala Pro Ser Ala Cys Thr Cys Leu Cys Leu His Phe Leu 
1               5                   10                  15      

Leu Leu Cys Phe Gln Val Gln Val Leu Val Ala Glu Glu Asn Val Asp 
            20                  25                  30          

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

Arg Lys Gln Leu Arg Leu Tyr Gln Leu Tyr Ser Arg Thr Ser Gly Lys 
    50                  55                  60                  

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

Asp Lys Tyr Ala Gln Leu Leu Val Glu Thr Asp Thr Phe Gly Ser Gln 
                85                  90                  95      

Val Arg Ile Lys Gly Lys Glu Thr Glu Phe Tyr Leu Cys Met Asn Arg 
            100                 105                 110         

Lys Gly Lys Leu Val Gly Lys Pro Asp Gly Thr Ser Lys Glu Cys Val 
        115                 120                 125             

Phe Ile Glu Lys Val Leu Glu Asn Asn Tyr Thr Ala Leu Met Ser Ala 
    130                 135                 140                 

Lys Tyr Ser Gly Trp Tyr Val Gly Phe Thr Lys Lys Gly Arg Pro Arg 
145                 150                 155                 160 

Lys Gly Pro Lys Thr Arg Glu Asn Gln Gln Asp Val His Phe Met Lys 
                165                 170                 175     

Arg Tyr Pro Lys Gly Gln Pro Glu Leu Gln Lys Pro Phe Lys Tyr Thr 
            180                 185                 190         

Thr Val Thr Lys Arg Ser Arg Arg Ile Arg Pro Thr His Pro Ala 
        195                 200                 205         


<210>  4
<211>  170
<212>  PRT
<213>  recombinant

<220>
<223>  Truncated FGF-18 (sprifermin)

<400>  4

Met Glu Glu Asn Val Asp Phe Arg Ile His Val Glu Asn Gln Thr Arg 
1               5                   10                  15      

Ala Arg Asp Asp Val Ser Arg Lys Gln Leu Arg Leu Tyr Gln Leu Tyr 
            20                  25                  30          

Ser Arg Thr Ser Gly Lys His Ile Gln Val Leu Gly Arg Arg Ile Ser 
        35                  40                  45              

Ala Arg Gly Glu Asp Gly Asp Lys Tyr Ala Gln Leu Leu Val Glu Thr 
    50                  55                  60                  

Asp Thr Phe Gly Ser Gln Val Arg Ile Lys Gly Lys Glu Thr Glu Phe 
65                  70                  75                  80  

Tyr Leu Cys Met Asn Arg Lys Gly Lys Leu Val Gly Lys Pro Asp Gly 
                85                  90                  95      

Thr Ser Lys Glu Cys Val Phe Ile Glu Lys Val Leu Glu Asn Asn Tyr 
            100                 105                 110         

Thr Ala Leu Met Ser Ala Lys Tyr Ser Gly Trp Tyr Val Gly Phe Thr 
        115                 120                 125             

Lys Lys Gly Arg Pro Arg Lys Gly Pro Lys Thr Arg Glu Asn Gln Gln 
    130                 135                 140                 

Asp Val His Phe Met Lys Arg Tyr Pro Lys Gly Gln Pro Glu Leu Gln 
145                 150                 155                 160 

Lys Pro Phe Lys Tyr Thr Thr Val Thr Lys 
                165                 170 

<210>  5
<211>  32
<212>  PRT
<213>  recombinant

<220>
<223>  calcitonin (salmon calcitonin)

<400>  5

Cys Ser Asn Leu Ser Thr Cys Val Leu Gly Lys Leu Ser Gln Glu Leu 
1               5                   10                  15      
His Lys Leu Gln Thr Tyr Pro Arg Thr Asn Thr Gly Ser Gly Thr Pro 
            20                  25                  30          


<210>  6
<211>  396
<212>  PRT
<213>  Homo Sapiens

<220>
<223>  human BMP-2

<400>  6

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


Val Leu Ser Glu Phe Glu Leu Arg Leu Leu Ser Met Phe Gly Leu Lys 
    50                  55                  60                  


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


Lys Arg His Val Arg Ile Ser Arg Ser Leu His Gln Asp Glu His Ser 
                245                 250                 255     


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  7
<211>  431
<212>  PRT
<213>  Homo Sapiens

<220>
<223>  human BMP-7

<400>  7
Met His Val Arg Ser Leu Arg Ala Ala Ala Pro His Ser Phe Val Ala 
1               5                   10                  15      


Leu Trp Ala Pro Leu Phe Leu Leu Arg Ser Ala Leu Ala Asp Phe Ser 
            20                  25                  30          


Leu Asp Asn Glu Val His Ser Ser Phe Ile His Arg Arg Leu Arg Ser 
        35                  40                  45              


Gln Glu Arg Arg Glu Met Gln Arg Glu Ile Leu Ser Ile Leu Gly Leu 
    50                  55                  60                  


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


Met Phe Met Leu Asp Leu Tyr Asn Ala Met Ala Val Glu Glu Gly Gly 
                85                  90                  95      


Gly Pro Gly Gly Gln Gly Phe Ser Tyr Pro Tyr Lys Ala Val Phe Ser 
            100                 105                 110         


Thr Gln Gly Pro Pro Leu Ala Ser Leu Gln Asp Ser His Phe Leu Thr 
        115                 120                 125             


Asp Ala Asp Met Val Met Ser Phe Val Asn Leu Val Glu His Asp Lys 
    130                 135                 140                 


Glu Phe Phe His Pro Arg Tyr His His Arg Glu Phe Arg Phe Asp Leu 
145                 150                 155                 160 


Ser Lys Ile Pro Glu Gly Glu Ala Val Thr Ala Ala Glu Phe Arg Ile 
                165                 170                 175     


Tyr Lys Asp Tyr Ile Arg Glu Arg Phe Asp Asn Glu Thr Phe Arg Ile 
            180                 185                 190         


Ser Val Tyr Gln Val Leu Gln Glu His Leu Gly Arg Glu Ser Asp Leu 
        195                 200                 205             


Phe Leu Leu Asp Ser Arg Thr Leu Trp Ala Ser Glu Glu Gly Trp Leu 
    210                 215                 220                 


Val Phe Asp Ile Thr Ala Thr Ser Asn His Trp Val Val Asn Pro Arg 
225                 230                 235                 240 


His Asn Leu Gly Leu Gln Leu Ser Val Glu Thr Leu Asp Gly Gln Ser 
                245                 250                 255     


Ile Asn Pro Lys Leu Ala Gly Leu Ile Gly Arg His Gly Pro Gln Asn 
            260                 265                 270         


Lys Gln Pro Phe Met Val Ala Phe Phe Lys Ala Thr Glu Val His Phe 
        275                 280                 285             


Arg Ser Ile Arg Ser Thr Gly Ser Lys Gln Arg Ser Gln Asn Arg Ser 
    290                 295                 300                 


Lys Thr Pro Lys Asn Gln Glu Ala Leu Arg Met Ala Asn Val Ala Glu 
305                 310                 315                 320 


Asn Ser Ser Ser Asp Gln Arg Gln Ala Cys Lys Lys His Glu Leu Tyr 
                325                 330                 335     


Val Ser Phe Arg Asp Leu Gly Trp Gln Asp Trp Ile Ile Ala Pro Glu 
            340                 345                 350         


Gly Tyr Ala Ala Tyr Tyr Cys Glu Gly Glu Cys Ala Phe Pro Leu Asn 
        355                 360                 365             


Ser Tyr Met Asn Ala Thr Asn His Ala Ile Val Gln Thr Leu Val His 
    370                 375                 380                 


Phe Ile Asn Pro Glu Thr Val Pro Lys Pro Cys Cys Ala Pro Thr Gln 
385                 390                 395                 400 


Leu Asn Ala Ile Ser Val Leu Tyr Phe Asp Asp Ser Ser Asn Val Ile 
                405                 410                 415     


Leu Lys Lys Tyr Arg Asn Met Val Val Arg Ala Cys Gly Cys His 
            420                 425                 430     


<210>  8
<211>  501
<212>  PRT
<213>  Homo Sapiens

<220>
<223>  human GDF-5

<400>  8

Met Arg Leu Pro Lys Leu Leu Thr Phe Leu Leu Trp Tyr Leu Ala Trp 
1               5                   10                  15      


Leu Asp Leu Glu Phe Ile Cys Thr Val Leu Gly Ala Pro Asp Leu Gly 
            20                  25                  30          


Gln Arg Pro Gln Gly Thr Arg Pro Gly Leu Ala Lys Ala Glu Ala Lys 
        35                  40                  45              


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


Tyr Gly Gly Gly Ala Thr Asn Ala Asn Ala Arg Ala Lys Gly Gly Thr 
65                  70                  75                  80  


Gly Gln Thr Gly Gly Leu Thr Gln Pro Lys Lys Asp Glu Pro Lys Lys 
                85                  90                  95      


Leu Pro Pro Arg Pro Gly Gly Pro Glu Pro Lys Pro Gly His Pro Pro 
            100                 105                 110         


Gln Thr Arg Gln Ala Thr Ala Arg Thr Val Thr Pro Lys Gly Gln Leu 
        115                 120                 125             


Pro Gly Gly Lys Ala Pro Pro Lys Ala Gly Ser Val Pro Ser Ser Phe 
    130                 135                 140                 


Leu Leu Lys Lys Ala Arg Glu Pro Gly Pro Pro Arg Glu Pro Lys Glu 
145                 150                 155                 160 


Pro Phe Arg Pro Pro Pro Ile Thr Pro His Glu Tyr Met Leu Ser Leu 
                165                 170                 175     


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


Lys Leu Glu Ala Gly Leu Ala Asn Thr Ile Thr Ser Phe Ile Asp Lys 
        195                 200                 205             


Gly Gln Asp Asp Arg Gly Pro Val Val Arg Lys Gln Arg Tyr Val Phe 
    210                 215                 220                 


Asp Ile Ser Ala Leu Glu Lys Asp Gly Leu Leu Gly Ala Glu Leu Arg 
225                 230                 235                 240 


Ile Leu Arg Lys Lys Pro Ser Asp Thr Ala Lys Pro Ala Ala Pro Gly 
                245                 250                 255     


Gly Gly Arg Ala Ala Gln Leu Lys Leu Ser Ser Cys Pro Ser Gly Arg 
            260                 265                 270         


Gln Pro Ala Ser Leu Leu Asp Val Arg Ser Val Pro Gly Leu Asp Gly 
        275                 280                 285             


Ser Gly Trp Glu Val Phe Asp Ile Trp Lys Leu Phe Arg Asn Phe Lys 
    290                 295                 300                 


Asn Ser Ala Gln Leu Cys Leu Glu Leu Glu Ala Trp Glu Arg Gly Arg 
305                 310                 315                 320 


Ala Val Asp Leu Arg Gly Leu Gly Phe Asp Arg Ala Ala Arg Gln Val 
                325                 330                 335     


His Glu Lys Ala Leu Phe Leu Val Phe Gly Arg Thr Lys Lys Arg Asp 
            340                 345                 350         


Leu Phe Phe Asn Glu Ile Lys Ala Arg Ser Gly Gln Asp Asp Lys Thr 
        355                 360                 365             


Val Tyr Glu Tyr Leu Phe Ser Gln Arg Arg Lys Arg Arg Ala Pro Leu 
    370                 375                 380                 


Ala Thr Arg Gln Gly Lys Arg Pro Ser Lys Asn Leu Lys Ala Arg Cys 
385                 390                 395                 400 


Ser Arg Lys Ala Leu His Val Asn Phe Lys Asp Met Gly Trp Asp Asp 
                405                 410                 415     


Trp Ile Ile Ala Pro Leu Glu Tyr Glu Ala Phe His Cys Glu Gly Leu 
            420                 425                 430         


Cys Glu Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn His Ala Val 
        435                 440                 445             


Ile Gln Thr Leu Met Asn Ser Met Asp Pro Glu Ser Thr Pro Pro Thr 
    450                 455                 460                 


Cys Cys Val Pro Thr Arg Leu Ser Pro Ile Ser Ile Leu Phe Ile Asp 
465                 470                 475                 480 


Ser Ala Asn Asn Val Val Tyr Lys Gln Tyr Glu Asp Met Val Val Glu 
                485                 490                 495     


Ser Cys Gly Cys Arg 
            500     


<210>  9
<211>  288
<212>  PRT
<213>  Homo Sapiens

<220>
<223>  human FGF-beta 

<400>  9

Met Val Gly Val Gly Gly Gly Asp Val Glu Asp Val Thr Pro Arg Pro 
1               5                   10                  15      


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


Pro Gly Ala Ala Ala Trp Glu Ala Ala Leu Pro Arg Arg Arg Pro Arg 
        35                  40                  45              


Arg His Pro Ser Val Asn Pro Arg Ser Arg Ala Ala Gly Ser Pro Arg 
    50                  55                  60                  


Thr Arg Gly Arg Arg Thr Glu Glu Arg Pro Ser Gly Ser Arg Leu Gly 
65                  70                  75                  80  


Asp Arg Gly Arg Gly Arg Ala Leu Pro Gly Gly Arg Leu Gly Gly Arg 
                85                  90                  95      


Gly Arg Gly Arg Ala Pro Glu Arg Val Gly Gly Arg Gly Arg Gly Arg 
            100                 105                 110         


Gly Thr Ala Ala Pro Arg Ala Ala Pro Ala Ala Arg Gly Ser Arg Pro 
        115                 120                 125             


Gly Pro Ala Gly Thr Met Ala Ala Gly Ser Ile Thr Thr Leu Pro Ala 
    130                 135                 140                 


Leu Pro Glu Asp Gly Gly Ser Gly Ala Phe Pro Pro Gly His Phe Lys 
145                 150                 155                 160 


Asp Pro Lys Arg Leu Tyr Cys Lys Asn Gly Gly Phe Phe Leu Arg Ile 
                165                 170                 175     


His Pro Asp Gly Arg Val Asp Gly Val Arg Glu Lys Ser Asp Pro His 
            180                 185                 190         


Ile Lys Leu Gln Leu Gln Ala Glu Glu Arg Gly Val Val Ser Ile Lys 
        195                 200                 205             


Gly Val Cys Ala Asn Arg Tyr Leu Ala Met Lys Glu Asp Gly Arg Leu 
    210                 215                 220                 


Leu Ala Ser Lys Cys Val Thr Asp Glu Cys Phe Phe Phe Glu Arg Leu 
225                 230                 235                 240 


Glu Ser Asn Asn Tyr Asn Thr Tyr Arg Ser Arg Lys Tyr Thr Ser Trp 
                245                 250                 255     


Tyr Val Ala Leu Lys Arg Thr Gly Gln Tyr Lys Leu Gly Ser Lys Thr 
            260                 265                 270         


Gly Pro Gly Gln Lys Ala Ile Leu Phe Leu Pro Met Ser Ala Lys Ser 
        275                 280                 285             



<210>  10
<211>  208
<212>  PRT
<213>  Homo Sapiens

<220>
<223>  human FGF-9 

<400>  10

Met Ala Pro Leu Gly Glu Val Gly Asn Tyr Phe Gly Val Gln Asp Ala 
1               5                   10                  15      


Val Pro Phe Gly Asn Val Pro Val Leu Pro Val Asp Ser Pro Val Leu 
            20                  25                  30          


Leu Ser Asp His Leu Gly Gln Ser Glu Ala Gly Gly Leu Pro Arg Gly 
        35                  40                  45              


Pro Ala Val Thr Asp Leu Asp His Leu Lys Gly Ile Leu Arg Arg Arg 
    50                  55                  60                  


Gln Leu Tyr Cys Arg Thr Gly Phe His Leu Glu Ile Phe Pro Asn Gly 
65                  70                  75                  80  


Thr Ile Gln Gly Thr Arg Lys Asp His Ser Arg Phe Gly Ile Leu Glu 
                85                  90                  95      


Phe Ile Ser Ile Ala Val Gly Leu Val Ser Ile Arg Gly Val Asp Ser 
            100                 105                 110         


Gly Leu Tyr Leu Gly Met Asn Glu Lys Gly Glu Leu Tyr Gly Ser Glu 
        115                 120                 125             


Lys Leu Thr Gln Glu Cys Val Phe Arg Glu Gln Phe Glu Glu Asn Trp 
    130                 135                 140                 


Tyr Asn Thr Tyr Ser Ser Asn Leu Tyr Lys His Val Asp Thr Gly Arg 
145                 150                 155                 160 


Arg Tyr Tyr Val Ala Leu Asn Lys Asp Gly Thr Pro Arg Glu Gly Thr 
                165                 170                 175     


Arg Thr Lys Arg His Gln Lys Phe Thr His Phe Leu Pro Arg Pro Val 
            180                 185                 190         


Asp Pro Asp Lys Val Pro Glu Leu Tyr Lys Asp Ile Leu Ser Gln Ser 
        195                 200                 205             





