                               SEQUENCE LISTING

<110> NOVARTIS AG
 
<120> PHARMACEUTICAL COMPOSITIONS AND PHARMACEUTICAL PRODUCTS OF 
      HETERODIMERIC HUMAN INTERLEUKIN-15 (HETIL-15)

<130> PAT058681-WO-PCT

<140>
<141>

<150> 63/013,801
<151> 2020-04-22

<160> 17    

<170> PatentIn version 3.5

<210> 1
<211> 162
<212> PRT
<213> Homo sapiens

<400> 1
Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr 
1               5                   10                  15      


Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His 
            20                  25                  30          


Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala 
        35                  40                  45              


Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
    50                  55                  60                  


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
65                  70                  75                  80  


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
                85                  90                  95      


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
            100                 105                 110         


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
        115                 120                 125             


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
    130                 135                 140                 


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
145                 150                 155                 160 


Thr Ser 
        


<210> 2
<211> 114
<212> PRT
<213> Homo sapiens

<400> 2
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210> 3
<211> 267
<212> PRT
<213> Homo sapiens

<400> 3
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


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


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr 
            100                 105                 110         


Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu 
        115                 120                 125             


Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala 
    130                 135                 140                 


Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr 
145                 150                 155                 160 


Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser 
                165                 170                 175     


Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln 
            180                 185                 190         


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


Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu 
    210                 215                 220                 


Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu 
225                 230                 235                 240 


Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg 
                245                 250                 255     


Asp Glu Asp Leu Glu Asn Cys Ser His His Leu 
            260                 265         


<210> 4
<211> 200
<212> PRT
<213> Homo sapiens

<400> 4
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


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


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr 
            100                 105                 110         


Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu 
        115                 120                 125             


Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala 
    130                 135                 140                 


Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr 
145                 150                 155                 160 


Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser 
                165                 170                 175     


Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln 
            180                 185                 190         


Pro Pro Gly Val Tyr Pro Gln Gly 
        195                 200 


<210> 5
<211> 170
<212> PRT
<213> Homo sapiens

<400> 5
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


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


Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      


Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr 
            100                 105                 110         


Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro 
        115                 120                 125             


Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr 
    130                 135                 140                 


Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser 
145                 150                 155                 160 


His Gln Pro Pro Gly Val Tyr Pro Gln Gly 
                165                 170 


<210> 6
<211> 8
<212> PRT
<213> Homo sapiens

<400> 6
Pro Gln Gly His Ser Asp Thr Thr 
1               5               


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

<400> 7
Pro Gln Gly His Ser Asp Thr 
1               5           


<210> 8
<211> 6
<212> PRT
<213> Homo sapiens

<400> 8
Pro Gln Gly His Ser Asp 
1               5       


<210> 9
<211> 5
<212> PRT
<213> Homo sapiens

<400> 9
Pro Gln Gly His Ser 
1               5   


<210> 10
<211> 4
<212> PRT
<213> Homo sapiens

<400> 10
Pro Gln Gly His 
1               


<210> 11
<211> 3
<212> PRT
<213> Homo sapiens

<400> 11
Pro Gln Gly 
1           


<210> 12
<211> 175
<212> PRT
<213> Homo sapiens

<400> 12
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


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


Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      


Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr 
            100                 105                 110         


Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro 
        115                 120                 125             


Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr 
    130                 135                 140                 


Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser 
145                 150                 155                 160 


His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr 
                165                 170                 175 


<210> 13
<211> 19
<212> PRT
<213> Homo sapiens

<400> 13
Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln Pro Pro Gly Val Tyr 
1               5                   10                  15      


Pro Gln Gly 
            


<210> 14
<211> 17
<212> PRT
<213> Homo sapiens

<400> 14
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys 
    


<210> 15
<211> 31
<212> PRT
<213> Homo sapiens

<400> 15
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser 
            20                  25                  30      


<210> 16
<211> 436
<212> PRT
<213> Artificial Sequence

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

<400> 16
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


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


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr 
            100                 105                 110         


Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu 
        115                 120                 125             


Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala 
    130                 135                 140                 


Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr 
145                 150                 155                 160 


Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser 
                165                 170                 175     


Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln 
            180                 185                 190         


Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Pro Lys Ser 
        195                 200                 205             


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
    210                 215                 220                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
225                 230                 235                 240 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                245                 250                 255     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            260                 265                 270         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        275                 280                 285             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    290                 295                 300                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
305                 310                 315                 320 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                325                 330                 335     


Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
            340                 345                 350         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        355                 360                 365             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    370                 375                 380                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
385                 390                 395                 400 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                405                 410                 415     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            420                 425                 430         


Ser Pro Gly Lys 
        435     


<210> 17
<211> 431
<212> PRT
<213> Artificial Sequence

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

<400> 17
Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


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


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr 
            100                 105                 110         


Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu 
        115                 120                 125             


Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala 
    130                 135                 140                 


Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr 
145                 150                 155                 160 


Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser 
                165                 170                 175     


Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln 
            180                 185                 190         


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


Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
    210                 215                 220                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
225                 230                 235                 240 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                245                 250                 255     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            260                 265                 270         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        275                 280                 285             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    290                 295                 300                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
305                 310                 315                 320 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                325                 330                 335     


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
            340                 345                 350         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        355                 360                 365             


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


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
385                 390                 395                 400 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                405                 410                 415     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            420                 425                 430     


