                               SEQUENCE LISTING

<110> NOVARTIS AG
 
<120> METHODS OF TREATING THYROID EYE DISEASE AND GRAVES' ORBITOPAHY 
      USING INTERLEUKIN-17 (IL-17) ANTAGONISTS

<130> PAT058784-WO-PCT

<140> PCT/US2021/038730
<141> 2021-06-23

<150> 63/042,721
<151> 2020-06-23

<160> 21    

<170> PatentIn version 3.5

<210> 1
<211> 5
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR1 = hypervariable region 1 of heavy chain of AIN457

<400> 1
Asn Tyr Trp Met Asn 
1               5   


<210> 2
<211> 17
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR2 = hypervariable region 2 of heavy chain of AIN457

<400> 2
Ala Ile Asn Gln Asp Gly Ser Glu Lys Tyr Tyr Val Gly Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210> 3
<211> 18
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR3 = hypervariable region 3 of heavy chain of AIN457

<400> 3
Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr Trp Tyr Phe 
1               5                   10                  15      


Asp Leu 
        


<210> 4
<211> 12
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR1' = hypervariable region 1 of light chain of AIN457

<400> 4
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala 
1               5                   10          


<210> 5
<211> 7
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR2' = hypervariable region 2 of light chain AIN457

<400> 5
Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210> 6
<211> 9
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR3' = hypervariable region 3 of light chain AIN457

<400> 6
Gln Gln Tyr Gly Ser Ser Pro Cys Thr 
1               5                   


<210> 7
<211> 381
<212> DNA
<213> Homo sapiens


<220>
<221> CDS
<222> (1)..(381)

<400> 7
gag gtg cag ttg gtg gag tct ggg gga ggc ttg gtc cag cct ggg ggg         48
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly           
1               5                   10                  15                

tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttt agt aac tat         96
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr           
            20                  25                  30                    

tgg atg aac tgg gtc cgc cag gct cca ggg aaa ggg ctg gag tgg gtg        144
Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val           
        35                  40                  45                        

gcc gcc ata aac caa gat gga agt gag aaa tac tat gtg ggc tct gtg        192
Ala Ala Ile Asn Gln Asp Gly Ser Glu Lys Tyr Tyr Val Gly Ser Val           
    50                  55                  60                            

aag ggc cga ttc acc atc tcc aga gac aac gcc aag aac tca ctg tat        240
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr           
65                  70                  75                  80            

ctg caa atg aac agc ctg aga gtc gag gac acg gct gtg tat tac tgt        288
Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Tyr Tyr Cys           
                85                  90                  95                

gtg agg gac tat tac gat att ttg acc gat tat tac atc cac tat tgg        336
Val Arg Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr Trp           
            100                 105                 110                   

tac ttc gat ctc tgg ggc cgt ggc acc ctg gtc act gtc tcc tca            381
Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser               
        115                 120                 125                       


<210> 8
<211> 127
<212> PRT
<213> Homo sapiens

<400> 8
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


Val Arg Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr Trp 
            100                 105                 110         


Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125         


<210> 9
<211> 327
<212> DNA
<213> Homo sapiens


<220>
<221> CDS
<222> (1)..(327)

<400> 9
gaa att gtg ttg acg cag tct cca ggc acc ctg tct ttg tct cca ggg         48
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly           
1               5                   10                  15                

gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt agc agc agc         96
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser           
            20                  25                  30                    

tac tta gcc tgg tac cag cag aaa cct ggc cag gct ccc agg ctc ctc        144
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu           
        35                  40                  45                        

atc tat ggt gca tcc agc agg gcc act ggc atc cca gac agg ttc agt        192
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser           
    50                  55                  60                            

ggc agt ggg tct ggg aca gac ttc act ctc acc atc agc aga ctg gag        240
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu           
65                  70                  75                  80            

cct gaa gat ttt gca gtg tat tac tgt cag cag tat ggt agc tca ccg        288
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro           
                85                  90                  95                

tgc acc ttc ggc caa ggg aca cga ctg gag att aaa cga                    327
Cys Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg                       
            100                 105                                       


<210> 10
<211> 109
<212> PRT
<213> Homo sapiens

<400> 10
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      


Cys Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg 
            100                 105                 


<210> 11
<211> 10
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR1-x = hypervariable domain x of heavy chain of AIN457

<400> 11
Gly Phe Thr Phe Ser Asn Tyr Trp Met Asn 
1               5                   10  


<210> 12
<211> 11
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR2-x = hypervariable domain of heavy chain x of AIN457

<400> 12
Ala Ile Asn Gln Asp Gly Ser Glu Lys Tyr Tyr 
1               5                   10      


<210> 13
<211> 23
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> CDR3-x = hypervariable domain x of heavy chain AIN457

<400> 13
Cys Val Arg Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr 
1               5                   10                  15      


Trp Tyr Phe Asp Leu Trp Gly 
            20              


<210> 14
<211> 215
<212> PRT
<213> Homo sapiens

<400> 14
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      


Cys Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg Thr Val Ala 
            100                 105                 110         


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


Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         


Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             


Ser Phe Asn Arg Gly Glu Cys 
    210                 215 


<210> 15
<211> 457
<212> PRT
<213> Homo sapiens

<400> 15
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


Val Arg Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr Trp 
            100                 105                 110         


Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Ala 
        115                 120                 125             


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


Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
145                 150                 155                 160 


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
                165                 170                 175     


Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
            180                 185                 190         


Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
        195                 200                 205             


Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg 
    210                 215                 220                 


Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
225                 230                 235                 240 


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                245                 250                 255     


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            260                 265                 270         


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        275                 280                 285             


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    290                 295                 300                 


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
305                 310                 315                 320 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                325                 330                 335     


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
            340                 345                 350         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        355                 360                 365             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    370                 375                 380                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
385                 390                 395                 400 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                405                 410                 415     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            420                 425                 430         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        435                 440                 445             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455         


<210> 16
<211> 7
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT LCDR1

<400> 16
Gln Ser Val Ser Ser Ser Tyr 
1               5           


<210> 17
<211> 3
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT LCDR2

<400> 17
Gly Ala Ser 
1           


<210> 18
<211> 9
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT LCDR3

<400> 18
Gln Gln Tyr Gly Ser Ser Pro Cys Thr 
1               5                   


<210> 19
<211> 8
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT HCDR1

<400> 19
Gly Phe Thr Phe Ser Asn Tyr Trp 
1               5               


<210> 20
<211> 8
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT HCDR2

<400> 20
Ile Asn Gln Asp Gly Ser Glu Lys 
1               5               


<210> 21
<211> 20
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<220>
<223> IMGT HCDR3

<400> 21
Val Arg Asp Tyr Tyr Asp Ile Leu Thr Asp Tyr Tyr Ile His Tyr Trp 
1               5                   10                  15      


Tyr Phe Asp Leu 
            20  


