                         SEQUENCE LISTING

<110>  Novo Nordisk A/S
 
<120>  Novel GLP-1 derivatives and uses thereof

<130>  150084WO01

<160>  24    

<170>  PatentIn version 3.5

<210>  1
<211>  31
<212>  PRT
<213>  Homo sapiens


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  1

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 Gly 
            20                  25                  30      


<210>  2
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  2

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


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


<210>  3
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue

<400>  3

His Gly 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 Gly 
            20                  25                  30      


<210>  4
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  4

His Trp 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 Gly 
            20                  25                  30      


<210>  5
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  5

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


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


<210>  6
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  6

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


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


<210>  7
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  7

His Trp 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 Arg Gly Arg Gly 
            20                  25                  30      


<210>  8
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  8

His Xaa 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 Arg Gly Arg Gly 
            20                  25                  30      


<210>  9
<211>  33
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(33)

<400>  9

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


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


Gly 
    


<210>  10
<211>  33
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(33)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  10

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


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


Gly 
    


<210>  11
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  11

His Trp 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 Arg Gly Arg Lys 
            20                  25                  30      


<210>  12
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  12

His Xaa 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 Arg Gly Arg Lys 
            20                  25                  30      


<210>  13
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue

<400>  13

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 Arg Gly Arg Gly 
            20                  25                  30      


<210>  14
<211>  582
<212>  PRT
<213>  Artificial sequence

<220>
<223>  dulaglutide


<220>
<221>  SIGNAL
<222>  (1)..(16)

<220>
<221>  CHAIN
<222>  (17)..(291)

<220>
<221>  MISC_FEATURE
<222>  (17)..(63)
<223>  GLP-1 analogue peptide including C-terminal linker  
       4xG-S-4xG-S-4xG-S-A

<220>
<221>  MISC_FEATURE
<222>  (64)..(291)
<223>  IgG-Fc part

<220>
<221>  DISULFID
<222>  (71)..(362)

<220>
<221>  DISULFID
<222>  (74)..(365)

<220>
<221>  SIGNAL
<222>  (292)..(307)

<220>
<221>  MISC_FEATURE
<222>  (308)..(354)
<223>  GLP-1 analogue peptide including C-terminal linker  
       4xG-S-4xG-S-4xG-S-A

<220>
<221>  CHAIN
<222>  (308)..(582)

<220>
<221>  MISC_FEATURE
<222>  (355)..(582)
<223>  IgG-Fc part

<400>  14

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 
1               5                   10                  15      


His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
            20                  25                  30          


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly 
        35                  40                  45              


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu 
    50                  55                  60                  


Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
65                  70                  75                  80  


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                85                  90                  95      


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            100                 105                 110         


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
        115                 120                 125             


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
    130                 135                 140                 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
145                 150                 155                 160 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
                165                 170                 175     


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            180                 185                 190         


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
        195                 200                 205             


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    210                 215                 220                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
225                 230                 235                 240 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
                245                 250                 255     


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
            260                 265                 270         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        275                 280                 285             


Ser Leu Gly Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly 
    290                 295                 300                 


Ala Leu Ala His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr 
305                 310                 315                 320 


Leu Glu Glu Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly 
                325                 330                 335     


Gly Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            340                 345                 350         


Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
        355                 360                 365             


Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
    370                 375                 380                 


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
385                 390                 395                 400 


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
                405                 410                 415     


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
            420                 425                 430         


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
        435                 440                 445             


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
    450                 455                 460                 


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
465                 470                 475                 480 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
                485                 490                 495     


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
            500                 505                 510         


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
        515                 520                 525             


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
    530                 535                 540                 


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
545                 550                 555                 560 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                565                 570                 575     


Leu Ser Leu Ser Leu Gly 
            580         


<210>  15
<211>  550
<212>  PRT
<213>  Artificial sequence

<220>
<223>  8W dulaglutide


<220>
<221>  CHAIN
<222>  (1)..(275)

<220>
<221>  MISC_FEATURE
<222>  (1)..(47)
<223>  GLP-1 analogue including C-terminal linker 4xG-S-4xG-S-4xG-S-A

<220>
<221>  MISC_FEATURE
<222>  (48)..(275)
<223>  IgG-Fc part

<220>
<221>  DISULFID
<222>  (55)..(330)

<220>
<221>  DISULFID
<222>  (58)..(333)

<220>
<221>  MISC_FEATURE
<222>  (276)..(322)
<223>  GLP-1 analogue including C-terminal linker 4xG-S-4xG-S-4xG-S-A

<220>
<221>  CHAIN
<222>  (276)..(550)

<220>
<221>  MISC_FEATURE
<222>  (323)..(550)
<223>  IgG-Fc part

<400>  15

His Trp 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 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 His Trp Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr 
        275                 280                 285             


Leu Glu Glu Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly 
    290                 295                 300                 


Gly Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Ala Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
                325                 330                 335     


Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
            340                 345                 350         


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
        355                 360                 365             


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
    370                 375                 380                 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
385                 390                 395                 400 


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                405                 410                 415     


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
            420                 425                 430         


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
        435                 440                 445             


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
    450                 455                 460                 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
465                 470                 475                 480 


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                485                 490                 495     


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
            500                 505                 510         


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
        515                 520                 525             


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
    530                 535                 540                 


Leu Ser Leu Ser Leu Gly 
545                 550 


<210>  16
<211>  36
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(35)

<400>  16

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


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


Gly Gly Ser Lys 
        35      


<210>  17
<211>  36
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(35)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  17

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


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


Gly Gly Ser Lys 
        35      


<210>  18
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  18

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


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


<210>  19
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  19

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


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


<210>  20
<211>  32
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(32)

<400>  20

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


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


<210>  21
<211>  32
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(32)

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Xaa at position 2 is Aib (2-Aminoisobutyric acid)

<400>  21

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


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


<210>  22
<211>  29
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(29)

<400>  22

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


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


<210>  23
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogue


<220>
<221>  mat_peptide
<222>  (1)..(31)

<400>  23

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


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


<210>  24
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Peptide (N-terminal extension)


<220>
<221>  PROPEP
<222>  (1)..(14)

<400>  24

Asp Val Lys Pro Gly Gln Pro Met Tyr Asp Asp Asp Asp Lys 
1               5                   10                  


