                         SEQUENCE LISTING

<110>  Eli Lilly and Company
 
<120>  Combination Therapy

<130>  X21145

<150>  US 62/616,455
<151>  2018-01-12

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  ACETYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)16-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  1

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Gln Ile Leu Ala Gln Val 
        35              


<210>  2
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  ACETYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  2

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Gln Ile Leu Ala Gln Val 
        35              


<210>  3
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  METHYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)16-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  3

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Gln Ile Leu Ala Gln Val 
        35              


<210>  4
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  METHYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  4

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Gln Ile Leu Ala Gln Val 
        35              


<210>  5
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  METHYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  5

Ile Val Thr Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Glu Ile Leu Ala Gln Val 
        35              


<210>  6
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  METHYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  6

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Glu Ile Leu Ala Gln Val 
        35              


<210>  7
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  METHYLATION

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  AMIDATION

<400>  7

Ile Val Thr Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Ile 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Glu Ile Leu Ala Gln Val 
        35              


<210>  8
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MOD_RES
<222>  (1)..(1)
<223>  Ile at position 1 is modified by either acetylation or 
       methylation at the N-terminus

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  Xaa at position 3 is Leu or Thr

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at position 16 is Leu or Ile

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Lys at position 29 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys side chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)z-CO2H
       , wherein z is 16 or 18

<220>
<221>  MISC_FEATURE
<222>  (33)..(33)
<223>  Xaa at position 33 is Gln or Glu

<220>
<221>  MOD_RES
<222>  (38)..(38)
<223>  Val at position 38 is optionally amidated

<400>  8

Ile Val Xaa Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Xaa 
1               5                   10                  15      


Glu Gln Glu Lys Gln Glu Lys Glu Lys Gln Gln Ala Lys Thr Asn Ala 
            20                  25                  30          


Xaa Ile Leu Ala Gln Val 
        35              


<210>  9
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa at position 30 is Arg or Gly

<220>
<221>  MISC_FEATURE
<222>  (47)..(47)
<223>  Xaa at position 47 is Ala or is deleted

<400>  9

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Xaa Gly Gly 
            20                  25                  30          


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Xaa Glu 
        35                  40                  45              


Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    50                  55                  60                  


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
65                  70                  75                  80  


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                85                  90                  95      


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            100                 105                 110         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
        115                 120                 125             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    130                 135                 140                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
145                 150                 155                 160 


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


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            180                 185                 190         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        195                 200                 205             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    210                 215                 220                 


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


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                245                 250                 255     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            260                 265                 270         


Ser Leu Gly 
        275 


<210>  10
<211>  275
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  10

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu 
        35                  40                  45              


Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    50                  55                  60                  


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
65                  70                  75                  80  


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                85                  90                  95      


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            100                 105                 110         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
        115                 120                 125             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    130                 135                 140                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
145                 150                 155                 160 


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


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            180                 185                 190         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        195                 200                 205             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    210                 215                 220                 


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


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                245                 250                 255     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            260                 265                 270         


Ser Leu Gly 
        275 


<210>  11
<211>  274
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  11

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly 
            20                  25                  30          


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ser 
        35                  40                  45              


Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
    50                  55                  60                  


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
65                  70                  75                  80  


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln 
                85                  90                  95      


Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            100                 105                 110         


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr 
        115                 120                 125             


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    130                 135                 140                 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile 
145                 150                 155                 160 


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


Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser 
            180                 185                 190         


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        195                 200                 205             


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    210                 215                 220                 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val 
225                 230                 235                 240 


Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met 
                245                 250                 255     


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            260                 265                 270         


Leu Gly 
        


<210>  12
<211>  38
<212>  PRT
<213>  Homo sapiens

<400>  12

Ile Val Leu Ser Leu Asp Val Pro Ile Gly Leu Leu Gln Ile Leu Leu 
1               5                   10                  15      


Glu Gln Ala Arg Ala Arg Ala Ala Arg Glu Gln Ala Thr Thr Asn Ala 
            20                  25                  30          


Arg Ile Leu Ala Arg Val 
        35              


