                         SEQUENCE LISTING

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

<130>  X21616

<150>  US 62/616,471
<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>  METHYLATION

<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 be 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>  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)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>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys sidechain with 
       ([2-(2-Amino-ethoxy)-ethoxy 
       ]-acetyl)2-(gamma-Glu)a-CO-(CH2)18-CO2H wherein a is 1

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is Phe

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is optionally amidated

<400>  9

Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Xaa Leu Asp Lys 
1               5                   10                  15      


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  10
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys sidechain with 
       ([2-(2-Amino-ethoxy)-ethoxy 
       ]-acetyl)2-(gamma-Glu)a-CO-(CH2)18-CO2H wherein a is 2

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is optionally amidated

<400>  10

Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Xaa Leu Asp Lys 
1               5                   10                  15      


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  11
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the Lys sidechain with 
       ([2-(2-Amino-ethoxy)-ethoxy 
       ]-acetyl)2-(gamma-Glu)a-CO-(CH2)18-CO2H wherein a is 1 or 2

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is Phe or 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is optionally amidated

<400>  11

Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Xaa Leu Asp Lys 
1               5                   10                  15      


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<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              


