                         SEQUENCE LISTING

<110>  ELI LILLY AND COMPANY
 
<120>  GLUCAGON RECEPTOR AGONISTS

<130>  X20416

<150>  62/246,199
<151>  2015-10-26

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  1

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser 
1               5                   10                  15      


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr 
            20                  25                  


<210>  2
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  2

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


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


<210>  3
<211>  37
<212>  PRT
<213>  Homo sapiens

<400>  3

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Ser 
1               5                   10                  15      


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr Lys Arg Asn 
            20                  25                  30          


Arg Asn Asn Ile Ala 
        35          


<210>  4
<211>  42
<212>  PRT
<213>  Homo sapiens

<400>  4

Tyr Ala Glu Gly Thr Phe Ile Ser Asp Tyr Ser Ile Ala Met Asp Lys 
1               5                   10                  15      


Ile His Gln Gln Asp Phe Val Asn Trp Leu Leu Ala Gln Lys Gly Lys 
            20                  25                  30          


Lys Asn Asp Trp Lys His Asn Ile Thr Gln 
        35                  40          


<210>  5
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa at pos. 7 is Thr or Leu

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       , wherein a is 1 or 2 and b is 14 to 24

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa at pos. 24 is Glu or Ala.

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa at pos. 29 is Thr or Glu.

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa at pos. 30 is either: absent, or a polypeptide selected from 
       the group consisting of GPSSGAPPPS and GPSSG, and the C-terminal 
       amino acid is optionally amidated

<400>  5

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


Lys Lys Ala Xaa Glu Phe Val Xaa Trp Leu Leu Glu Xaa Xaa 
            20                  25                  30  


<210>  6
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 2 and b is 16.

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at pos. 39 is amidated as a C-terminal primary amide

<400>  6

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


Lys Lys Ala Xaa Glu Phe Val Glu Trp Leu Leu Glu Thr Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  7
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 2 and b is 18

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at pos. 39 is amidated as a C-terminal primary amide

<400>  7

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


Lys Lys Ala Xaa Glu Phe Val Glu Trp Leu Leu Glu Thr Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  8
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 2 and b is 16

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at pos. 39 is amidated as a C-terminal primary amide

<400>  8

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


Lys Lys Ala Xaa Glu Phe Val Glu Trp Leu Leu Glu Thr Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  9
<211>  34
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 2 and b is 16

<220>
<221>  MOD_RES
<222>  (34)..(34)
<223>  The Gly at pos. 34 is amidated as a C-terminal primary amide

<400>  9

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


Lys Lys Ala Xaa Glu Phe Val Glu Trp Leu Leu Glu Thr Gly Pro Ser 
            20                  25                  30          


Ser Gly 
        


<210>  10
<211>  34
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 2 and b is 18

<220>
<221>  MOD_RES
<222>  (34)..(34)
<223>  Gly at pos. 34 is amidated as a C-terminal primary amide

<400>  10

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


Lys Lys Ala Xaa Glu Phe Val Glu Trp Leu Leu Glu Thr Gly Pro Ser 
            20                  25                  30          


Ser Gly 
        


<210>  11
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 1 and b is 16

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Glu at pos. 29 is C-terminal acid

<400>  11

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


Lys Lys Ala Xaa Glu Phe Val Ala Trp Leu Leu Glu Glu 
            20                  25                  


<210>  12
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H
       wherein a is 1 and b is 18

<220>
<221>  MOD_RES
<222>  (29)..(29)
<223>  Glu at pos. 29 is C-terminal acid.

<400>  12

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


Lys Lys Ala Xaa Glu Phe Val Ala Trp Leu Leu Glu Glu 
            20                  25                  


<210>  13
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at pos. 13 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO(CH2)b-CO2H 
       wherein a is 1 or 2 and b is 10 to 20

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

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

<400>  13

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  14
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at pos. 13 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO(CH2)b-CO2H 
       wherein a is 2 and b is 18

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

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at pos. 39 is amidated as a C-terminal primary amide

<400>  14

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  15
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at pos. 13 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa at pos. 20 is Lys which 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)a-CO(CH2)b-CO2H 
       wherein a is 1 and b is 18

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at pos. 29 is amidated as a C-terminal primary amide

<400>  15

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  16
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa at pos. 7 is Thr or Leu

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa as pos. 20 is Lys which 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)a-CO-(CH2)b-CO2H, wherein a is 2 and b is 14 to 24

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa as pos. 24 is Glu

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa as pos. 29 is Thr

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa as pos. 30 is a peptide selected from the group consisting of
       GPSSGAPPPS and GPSSG;and the C-terminal amino acid is amidated

<400>  16

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


Lys Lys Ala Xaa Glu Phe Val Xaa Trp Leu Leu Glu Xaa Xaa 
            20                  25                  30  


<210>  17
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at pos. 2 is alpha Aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa at pos. 7 is Thr

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa at pos. 16 is alpha Aminoisobutyric acid

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Xaa as pos. 20 is Lys which is chemically modified through 
       conjugation to the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma 
       Glu)a-CO-(CH2)b-CO2H, wherein a is 1 and b is 14 to 24

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa at pos. 24 is Ala

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa at pos. 29 is Glu

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa at pos. 30 is absent

<400>  17

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


Lys Lys Ala Xaa Glu Phe Val Xaa Trp Leu Leu Glu Xaa Xaa 
            20                  25                  30  


